Age-related reduction in visually evoked cerebral blood flow responses.

The influence of aging on photoreactive flow changes in the posterior cerebral artery (PCA) was investigated in 38 healthy volunteers aged 20-81 years. Mean blood flow velocity (MBFV) was measured at rest and during 10-Hz photic stimulation by transcranial Doppler sonography. The amplitude of the evoked flow response significantly decreased with age (r = -0.39; P < 0.001). In a group of elderly subjects (60-81 years), the evoked blood flow velocity increase was 10.8 +/- 2.7%, which is less than in young subjects aged 20-39 years (14.7 +/- 4.3%; P = 0.001). We conclude that normal aging affects photoreactive flow changes in the occipital lobe. This may limit the application of functional imaging studies based on measurements of blood flow changes in the elderly.

Residual function in motor cortex contralateral to amputated hand.

OBJECTIVE: To investigate residual function of the motor cortex corresponding to the hand of the amputated arm (MCamp). METHODS: Focal transcranial magnetic stimulation (TMS) of MCamp was performed in 10 patients 22 to 52 years after arm amputation to inhibit tonic muscle contraction in the intact hand ipsilateral to cortex stimulation. RESULTS: In all patients, onset latency, degree, and duration of this inhibition were normal. CONCLUSION: The presence of motor inhibition in the residual hand of amputees originating from the hand motor representation of MCamp indicates residual cortical motor representation of the lost hand irrespective of whether the effect is mediated by commissural or ipsilateral corticospinal connections.

Long-term reorganization of motor cortex outputs after arm amputation.

OBJECTIVE: To investigate the reorganization of the corticospinal system long after arm amputation at different levels. METHODS: Focal transcranial magnetic stimulation (TMS) was performed in 15 patients 21 to 65 years after arm amputation at the level of the forearm, upper arm, or shoulder. Cortically elicited electromyographic responses were investigated in muscles immediately proximal to the stump. TMS was performed on a skull surface grid overlying the motor cortex. The response threshold, number of effective stimulation sites, and the sum of the amplitudes elicited at these sites were evaluated for slightly contracted muscles. RESULTS: Seven of eight patients with forearm amputation had larger stimulation effects in the biceps supplied by the motor cortex contralateral to amputation, as indicated by variable patterns of lowered response thresholds, increased response amplitudes, or increased numbers of effective stimulation sites. In seven patients with a more proximal amputation, the motor responses were investigated in the deltoid and trapezoid muscle. In only two of them, the motor cortex contralateral to amputation showed an increased excitability. Three patients presented with a higher excitability of the motor cortex contralateral to the intact arm and two with a balanced type of excitability. CONCLUSION: Reorganization of the motor system can be present more than 20 years after amputation. Furthermore, differential patterns of reorganized corticospinal output were found for different stump muscles, which might be due to varying amounts of ipsilateral corticospinal projections.

Correlates of disability in multiple sclerosis detected by transcranial magnetic stimulation.

OBJECTIVE: To study the usefulness of corticospinally mediated excitatory responses and transcallosal inhibition (TI) elicited by transcranial magnetic stimulation (TMS) as a surrogate marker of disability in patients with different courses of MS. METHODS: Focal TMS of the motor cortex was performed in 118 patients with MS (96 with relapsing-remitting, 19 with primary progressive, and three with secondary progressive disease) who had an Expanded Disability Status Scale (EDSS) score between 0 and 6.5 and in 35 normal subjects. Central motor latencies (CML) and TI (onset latency, duration) were investigated. The Spearman rank correlation was used for statistical analysis. RESULTS: TMS disclosed prolonged CML in 52.5% and abnormal TI in 61% of the patients. In all patients the EDSS correlated with the frequency of abnormal TI (r = 0.58, p < 0.01) and abnormal CML (r = 0.51, p < 0.01). In patients with primary progressive MS (EDSS 1.5 to 6.5) the frequency of TI abnormalities correlated with EDSS (r = 0.65, p < 0.01) whereas CML did not. Delayed corticospinal responses in hand muscles always led to abnormal TI. CONCLUSIONS: The combination of central motor latencies and transcallosal inhibition evoked by transcranial magnetic stimulation yields objective data to estimate disease progression in MS as assessed by the EDSS.

Corticospinal excitability in human sleep as assessed by transcranial magnetic stimulation.

The excitability of the corticospinal system was studied in 23 healthy subjects in sleep stages NREM2, NREM4, REM, and wakefulness using transcranial magnetic stimulation. Assessment of motor thresholds, stimulus-response curves, and latencies of motor evoked potentials shows activation of the fast-conducting corticospinal fibers in all sleep stages and a neuronal recruitment pattern similar to wakefulness, however, at a lower level of excitability and with significant differences between sleep stages.

MRI study of human brain exposed to high-dose repetitive magnetic stimulation of visual cortex.

T1-, T2-, and diffusion-weighted MRI was used to determine whether repetitive transcranial magnetic stimulation (rTMS) affects the blood-brain barrier or induces localized brain edema. In 11 healthy individuals, 1,200 to 3,800 stimuli were applied over the visual cortex of one hemisphere in series of 5-, 10-, or 20-Hz stimulus trains. MRI performed 6 minutes to 6 hours after rTMS did not show pathologic changes in conventional MRI sequences, after application of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), or by determining apparent diffusion coefficients.

Peroxide-dependent amino acid oxidation and chemiluminescence catalysed by magnesium-pyridoxal phosphate-glutamate complex.

Magnesium-pyridoxal-5'-phosphate-glutamate (MPPG) has been shown to ameliorate atherosclerotic symptoms in rabbits. In vitro, MPPG in the presence of peroxides such as cholesterolhydroperoxide or cumene hydroperoxide and Mn2+ ions produces "excited states" measurable as chemiluminescence or ethylene release from 1-aminocyclopropane-1-carboxylic acid (ACC). The reactions are stimulated synergistically by unsaturated fatty acids. Pyridoxal phosphate exhibits similar properties, but can be differentiated from the activities of MPPG or the sum of the components present in MPPG.

The important role of fitness determination and stress testing in predicting coronary incidence.

The question of whether there is some effect of status of cardiorespiratory fitness and exercise ECG abnormalities on occurrence of CHD other than their effect on the risk factors of serum cholesterol, blood pressure, glucose, and smoking seems to have been answered in the affirmative by this study. The relative prognostic importance of the measures considered here, the role of exercise, and the interrelationships between fitness, exercise, other risk factors, and CHD provide many interesting hypotheses for continued study. A future investigation will involve a large prospective study in which the risk function to be derived would include stress ECG and treadmill performance as predictor variables. The retrospective approach reported in this paper had certain limitations. It did, however, permit demonstration of new results because, essentially for the first time, all of the important risk factors are measured in the study population and can be evaluated simultaneously.

Functional magnetic resonance imaging shows localized brain activation during serial transcranial stimulation in man.

Area and depth penetration of transcranial stimulation methods such as transcranial electrical stimulation (TES) are poorly defined. We investigated the feasibility of a simultaneous TES and fMRI measurement. The aim was to compare the signal intensity changes measured using BOLD fMRI during sequential finger movement with the signal response during artificial transcranial stimulation. Tes induced contralateral finger contractions and in T2* weighted images a transient signal increase was observed in the area underlying the electrodes. Compared with the signal obtained during sequential finger movements, the area activated by TES was more localized, signal amplitude, was smaller and there was no post-stimulus undershoot. These data indicate that TES induces a local blood flow increase associated with a drop in the concentration of deoxyhaemoglobin.

Wilson's disease: normalisation of cortically evoked motor responses with treatment.

A newly diagnosed patient with Wilson's disease is reported in whom the only clearly pathological neurophysiological findings before treatment were abnormal electromyographic (EMG) responses evoked by transcranial magnetic brain stimulation. Serial examinations over 10 months following commencement of treatment with D-penicillamine revealed normalisation of EMG responses. Pathophysiologically, the initially abnormal EMG responses probably resulted from reversible impairment of impulse propagation along cortico-motor-neuronal pathways and/or a reduced excitability of cortical cells due to impaired function of the basal ganglia.

Investigation of unilateral facial weakness: magnetic stimulation of the proximal facial nerve and of the face-associated motor cortex.

Twenty-four patients with unilateral facial weakness of various aetiologies were investigated using a magnetic stimulator to stimulate the proximal segment of the facial nerve directly (short latency response) and also to activate the facial motoneurons bilaterally via corticonuclear pathways by placing the stimulating coil over the motor cortex (long latency responses). Electromyographic recordings were taken from both mentalis muscles using concentric needle electrodes. Seventeen patients were investigated at various times after onset of idiopathic facial palsy (Bell's palsy). In the acute stage (less than 5 days after onset) short and long latency responses on the paretic side were abnormal, being absent in all but one patient, in whom the short latency response was delayed. These abnormal responses were the earliest neurographic correlate for nerve conduction block. In 4 out of 9 patients seen up to 30 days after onset of palsy, trans-synaptically evoked long latency responses were absent. In patients examined more than 2 months after onset, long latency responses could always be obtained and, in 5 of 8 patients, short latency responses could also be elicited, indicating a return of the direct excitability of the nerve. Five patients with cerebral hemisphere lesions causing mild unilateral facial weakness had absent long latency responses when stimulating over the affected hemisphere, but normal bilateral long latency responses following stimulation over the unaffected cerebral hemisphere; short latency responses were normal. Magnetic stimulation of the brain and of the facial nerve can differentiate between central and peripheral causes of unilateral facial weakness and may prove useful in the early assessment of the degree of conduction block in Bell's palsy.

Morphology of acallosal brains as assessed by MRI in six patients leading a normal daily life.

The pattern of anatomical features of the brain revealed by magnetic resonance imaging (MRI) is described in six patients incidentally identified as having acallosal brains. The complex of morphological features associated with complete agenesis of the corpus callosum included lateral displacement of slitlike anterior horns of the lateral ventricles (bullhorn-like shape), dilatation of the posterior horns of the lateral ventricles, absence of the septum pellucidum, lateral displacement of the cingulate gyri, complete separation of fornices and the presence of the anterior commissure and longitudinal callosal bundles (Probst's bundles). No compensatory enlargement of the anterior commissure was seen in the patients. The planimetrically measured cross-sectional areas of the anterior commissures were between 2.0 and 4.2 mm2 (mean 3.1) (in ten normal subjects they were 4.5, SD 0.4; range 3.8-5.2 mm2) and were reduced in four and normal in two patients. Inconstant morphological features were an absence of the posterior commissure and a radial pattern of the sulci and gyri on the medial aspect of the hemispheres. Conventional clinical testing revealed no abnormalities except a slight impairment of walking heel-to-toe in two patients. None of the patients had subjective restrictions of activities of daily life, which shows the efficacy of unknown compensatory processes.

Complex repetitive discharges in the iliopsoas muscle.

A prospective electromyographic investigation of lower limb muscles in patients with different neurogenic disorders showed that complex repetitive discharges (CRD) were observed predominantly and often only in the iliopsoas muscle. Analysis of the EMG findings in acute and chronic lesions shows that CRD are a feature of a chronic proximal motor axon lesion. Furthermore, the frequently focal occurrence of CRD in the iliopsoas muscle in clinically distal diabetic polyneuropathies suggests that this muscle and its nerves represent a locus minoris resistentiae.

Impairment of callosal and corticospinal system function in adolescents with early-treated phenylketonuria: a transcranial magnetic stimulation study.

The transcranial activation and the conduction properties of corticospinal and callosal neurons were investigated in 12 early-treated adolescents (aged 17.3, SD 3.5 years; range 14-27 years) with phenylketonuria (PKU) by focal transcranial magnetic stimulation (fTMS) of the motor cortex. The patients had no functionally relevant motor disturbances in daily life or on clinical testing. Corticospinally mediated excitatory (response thresholds, amplitudes, central motor latencies) and inhibitory [duration of postexcitatory inhibition (PI)] effects of fTMS were investigated in contralateral hand muscles. Transcallosal inhibition (TI) (onset latency, duration, transcallosal latency) of tonic electromyographic (EMG) activity was tested in ipsilateral muscles. Peripheral motor latencies were determined for responses elicited by magnetic stimulation over cervical nerve roots. Ten normal subjects served as controls. Since in all PKU patients, central and peripheral motor latencies were normal, no neurophysiological indication of a demyelination of corticospinal or peripheral motor fibres was found. However, cortical thresholds of corticospinally mediated responses were increased (52.1, SD 11.6% versus 35.0, SD 7.4% of maximum stimulator output; P < 0.05; n = 24 hands) and their amplitudes reduced (2.9, SD 1.4 mV versus 6.1, SD 1.5 mV, P < 0.05). The duration of PI was shortened (132, SD 53 ms versus 178, SD 57 ms; P < 0.05). TI was absent in 37.5% of the investigated hands or tended to be weak. When TI was present, its onset latencies (38.0, SD 3.6 ms versus 34.7, SD 3.3 ms) and transcallosal latencies were prolonged (18.5, SD 3.8 ms versus 14.8, SD 3.2 ms), while its duration was normal. These abnormal excitatory and inhibitory effects of fTMS suggest a reduced susceptibility of cortical excitatory and inhibitory neuronal structures compatible with a loss of neurons or a rarefication of their dendrites.

Callosal and corticospinal tract function in patients with hydrocephalus: a morphometric and transcranial magnetic stimulation study.

In 15 patients with symptomatic hydrocephalus, pressure-induced morphological changes of the brain and the function of callosal and corticospinal fibres were studied. Morphometry of the corpus callosum (CC) was performed on midsagittal MR images. Focal transcranial magnetic stimulation of the motor cortex was used to assess simultaneously excitatory motor responses in contralateral hand muscle (corticospinally mediated effect) and inhibition of tonic EMG activity in ipsilateral hand muscles (transcallosal inhibition (TI) of the contralateral motor cortex). Before a shunt operation, the midsagittal area of the CC was reduced by 34% on average. The height and, to a lesser degree the length, of the CC were increased before the shunt operation. Thresholds and central motor latencies of corticospinally mediated responses were normal, response amplitudes were smaller than in normal subjects. Motor thresholds increased from 38, SD 5 to 52, SD 8% (P < 0.01) within 7 days after ventricular drainage, reflecting the increase in the distance between stimulation coil and brain. The threshold increase paralleled a restoration of normal anatomical conditions within 7 days after shunt operation and the improvement of motor symptoms and might be a predictor of successful decompression. Transcallosal inhibition could be elicited in all patients. The measurements of TI lay within the normal range except the duration, which was prolonged in 73% of 15 patients before shunt operation as a probable indicator of an increased dispersion of callosal conduction. The normalization of the area and shape of the CC after shunt operation and the normal corticospinal and callosal conduction times exclude degeneration, demyelination or functional block of a large proportion of callosal or corticospinal tract fibres or a substantial loss of nerve cells in motor cortex.

Abnormal postexcitatory and interhemispheric motor cortex inhibition in writer's cramp.

Focal transcranial magnetic stimulation (TMS) of the motor cortex was used to study excitatory and inhibitory stimulation effects in 25 patients with writer's cramp and 25 healthy volunteers. We investigated excitatory and inhibitory corticospinally mediated motor effects in muscles contralateral to the stimulation side as well as interhemispheric inhibition of tonic motor activity in muscles ipsilateral to stimulation. Motor evoked potentials (MEPs) were recorded from both first dorsal interosseus muscles. Motor thresholds at rest and amplitudes and latencies of MEPs obtained during maximal contraction were always bilaterally normal. The duration of postexcitatory inhibition was significantly shortened (168+/-55 vs. 198+/-39 ms in normal subjects, P=0.001) and the duration of interhemispheric inhibition prolonged (30.3+/-6.6 vs. 26+/-3.9 ms in normal subjects, P < 0.001). Both observations would be compatible with a decreased inhibition of corticospinal and transcallosal outputs of the motor cortex. The results were not influenced by fatigue effects. Abnormal motor cortex inhibition seems to be a generalized phenomenon in writer's cramp since it was detected in both hemispheres and during a simple isometric motor task which did not evoke dystonic symptoms.

Motor responses evoked by magnetic brain stimulation in psychogenic limb weakness: diagnostic value and limitations.

The latencies and amplitudes of responses evoked by magnetic brain stimulation (magnetic evoked potentials, MEP) in the first dorsal interosseus and the anterior tibial (TA) muscles were investigated in 15 patients with psychogenic limb weakness and in 50 patients with limb weakness due to established organic central nervous system disease. Of the patients with psychogenic limb weakness, 3 presented with upper limb monopareses, 2 with lower limb monoparesis, 4 with hemipareses, 4 with parapareses and 2 with paraparesis. All patients with psychogenic weakness had MEP in arm and leg muscles with latencies within the normal range. MEP amplitudes were also normal except for 1 patient in whom the response amplitude in the TA of the plegic limb was reduced. In patients with limb weakness due to established organic disease, MEP were frequently but not invariably abnormal. In patients with plegic (i.e. completely paretic, MRC grade 0) muscles due to organic disease, MEP always were clearly abnormal. Normal MEP were sometimes elicited from paretic muscles, more commonly in association with cerebral hemisphere lesions than with spinal lesions. We conclude that psychogenic limb weakness is associated with normal MEP. However, normal MEP in mildly paretic muscles do not definitely exclude organic pathology.

Influence of pulse configuration and direction of coil current on excitatory effects of magnetic motor cortex and nerve stimulation.

UNLABELLED: This paper describes the influence of pulse configuration and current direction on the excitation of the hand-associated motor cortex and the median nerve by magnetic stimulation. Monophasic and biphasic current pulses with the same peak rise time of 80 micros and a maximum rate of current change (dI/dt) were discharged through an eight-shaped coil of the stimulator used (Dantec MagPro). Two current directions with opposite orientation in the coil axis were studied. FINDINGS: (1) for both, cortex and nerve stimulation, biphasic stimuli were more effective and elicited compound muscle action potentials (CMAPs) with lower thresholds and larger amplitudes. (2) Using biphasic pulses the direction of the currents in the first phase of the pulse did not influence the CMAP amplitude. (3) Using monophasic pulses induced currents oriented postero-anteriorly in the motor cortex or orthodromically along the nerve axis elicited larger CMAPs than currents in the opposite orientation. (4) Pulse configuration did not influence the CMAP-latencies and by this the stimulation site (cortex, nerve). CONCLUSION: Monophasic stimuli are useful to investigate excitation effects which are dependent on the current direction. The application of biphasic stimuli with their stronger excitation effects might be advantageous when patients with high cortical thresholds or deep lying nerves shall be investigated.

Pseudo-bilateral hand motor responses evoked by transcranial magnetic stimulation in patients with deep brain stimulators.

OBJECTIVES: In 3 of 5 patients with dystonia and bilaterally implanted deep brain stimulating electrodes, focal transcranial magnetic stimulation (TMS) of one motor cortex elicited bilateral hand motor responses. The aim of this study was to clarify the origin of these ipsilateral responses. METHODS: TMS and electrical stimulation of corticospinal fibres by the implanted electrodes were performed and the evoked hand motor potentials were analysed. RESULTS: In comparison with responses elicited by contralateral motor cortex stimulation, ipsilateral responses were smaller in amplitude (3.0+/-1.4 versus 5.8+/-1.5 mV), had shorter peak latencies (first negative peak: 20.9+/-0.8 versus 25.1+/-0.4 ms) and were followed by a shorter-lasting silent period (46+/-4 versus 195+/-35 ms). Ipsilateral responses following TMS had similar peak latencies to responses elicited subcortically by deep brain stimulation (DBS) (20.4+/-0.9 ms). CONCLUSIONS: Hand motor responses ipsilateral to TMS result from a subcortical activation of corticospinal fibres, via the implanted electrode in the other hemisphere, secondary to currents induced by TMS in subcutaneous wire loops that underlie the magnetic coil. Studies of TMS in patients with DBS have to take this potential source of confounding into account.

Patterns of abnormal motor cortex excitability in atypical parkinsonian syndromes.

OBJECTIVE: Multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal-ganglionic degeneration (CBGD) are all clinically characterized by an akinetic-rigid syndrome together with a variety of additional signs. We hypothesised that these atypical parkinsonian syndromes (APS) will show distinctive patterns in their motor output upon transcranial magnetic stimulation (TMS) due to their different underlying anatomico-functional deficits. METHODS: We performed single and paired-pulse TMS and assessed inhibitory and excitatory response parameters from the first dorsal interosseus muscles in 13 patients with MSA, 18 with PSP, 13 with CBGD, 15 patients with Parkinson's disease and 17 healthy subjects. RESULTS: PSP and MSA patients had significantly enlarged response amplitudes at rest, reduced intracortical inhibition (ICI) and prolonged ipsi- and contralateral silent periods, whereas CBGD patients showed significantly increased motor thresholds, smaller response amplitudes at rest, shortened contralateral silent period, reduced transcallosal inhibition and a reduced ICI. In 22% of APS patients ipsilateral motor responses occurred in upper limb muscles irrespective of the underlying disease. CONCLUSIONS: Our results indicate that motor cortex disinhibition is predominant in patients with PSP and MSA. In CBGD more severe neuronal cell loss in the motor cortex itself may lead to hypoexcitability of corticospinal and transcallosal pathways.