Beta-blocker migraine prophylaxis affects the excitability of the visual cortex as revealed by transcranial magnetic stimulation.

The objective of this study is to assess effects of beta-blocker migraine prophylaxis on cortical excitability determined by transcranial magnetic stimulation (TMS). Phosphene and motor thresholds (PT, MT) were investigated in 29 patients with migraine, in 15 of them prior to and following preventive medication with metoprolol and in 14 patients without prophylaxis. Following prophylaxis headache frequency significantly decreased (p = 0.005) and mean PT were significantly increased (51.5 ± 7.5 vs. 63.6 ± 8.4%) compared to patients without preventive treatment (53.7 ± 5.3 vs. 52.3 ± 6.3%; p = 0.040). Mean MT did not significantly differ either between groups or due to treatment. In the group of all patients, a significant inverse correlation between headache frequency and the level of PT was found (R = -0.629; p < 0.01). There was, however, no significant correlation in the subgroups of patients. We conclude that (a) clinical efficacy of beta-blocker treatment in migraine could be (at least partly) linked to its ability to modulate the excitability of the visual cortex and (b) the PT determined by TMS appears suitable to assess the effects of prophylaxis on cortical excitability in the individual patient. This may be useful in clinical trials investigating migraine preventive drugs.

MRI study of human brain exposed to weak direct current stimulation of the frontal cortex.

OBJECTIVE: To determine whether weak transcranial direct current stimulation (tDCS), which is an interesting new tool inducing prolonged cortical excitability shifts in humans, induces brain edema, disturbance of the blood-brain barrier or structural alterations of the brain detectable by magnetic resonance imaging (MRI). METHODS: In 10 healthy individuals, tDCS, which is known to alter cortical excitability for about 1 h, was applied over motor and pre-frontal cortices. contrast-enhanced t1-, t2-, and diffusion-weighted mri was performed immediately before, 30 and 60 min after tdcs. RESULTS: MRI performed 30 and 60 min after tDCS did not show pathological signal alterations in pre- and post-contrast-enhanced T1-weighted and diffusion-weighted MR sequences. CONCLUSIONS: tDCS protocols which are known to result in cortical excitability changes persisting for an hour after stimulation do not induce brain edema or alterations of the blood-brain barrier or cerebral tissue detectable by MRI. SIGNIFICANCE: These results deliver further evidence for the safety of the currently applied tDCS protocols in humans.

Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophrenia.

BACKGROUND: Focal transcranial magnetic stimulation (TMS) of the motor cortex was used to study two cortically activated inhibitory neuronal mechanisms that suppress ongoing tonic voluntary electromyographic activity in contralateral (postexcitatory inhibition [PI]) and ipsilateral (transcallosal inhibition [TI]) hand muscles. The PI follows the corticospinally mediated excitatory motor response (MEP) and is influenced by dopaminergic neurotransmission. TI reflects transcallosally mediated inhibition of the contralateral motor cortex, leading to motor inhibition in muscles ipsilateral to stimulation. PI and TI were studied to explore whether dopaminergic neurotransmission or interhemispheric transfers are altered in schizophrenia. METHODS: TMS was performed in 16 patients with this disease and in 16 healthy control subjects. Surface electromyographic activity was recorded bilaterally from the first dorsal interosseous muscle during a sustained strong isometric contraction. RESULTS: When compared with the findings in healthy subjects, patients with schizophrenia had a significantly longer PI and TI. The changes of the PI support the notion of an overactivity of the central dopaminergic system in schizophrenia. CONCLUSION: The prolonged TI suggests an abnormal activation of interhemispheric connections between the motor cortices and may be related to previously reported pathology of the corpus callosum in schizophrenic patients.

Evaluation of cortical excitability by motor and phosphene thresholds in transcranial magnetic stimulation.

Motor threshold (MT), as determined by transcranial magnetic stimulation (TMS), is used as a parameter of cortex excitability. In TMS with single or repetitive pulses, stimulus intensities in general are referred to the individual MT, although it is unclear whether MT also reflects the excitability of nonmotor cortical areas such as the visual cortex. Visual cortex excitability can be assessed by thresholds for eliciting phosphenes (phosphene threshold, PT) following TMS over the occipital cortex. The question of a different efficacy of TMS pulses in distinct cortical areas was approached by comparing motor and phosphene thresholds using single-pulse TMS applied to the primary motor and visual cortex. The aim of the study was to clarify, whether MT and PT correlate with each other and whether MT possibly serves as a reasonable measure for the excitability of the visual cortex. In 32 healthy volunteers, TMS with biphasic single pulses was applied over the motor and visual cortex with a figure of eight-shaped coil connected to a Dantec MagPro stimulator. MT and PT were individually measured (percent of maximal stimulator output). Mean PT (61.4+/-11.7%) was significantly higher than mean MT (39.4+/-5.9%) (p=0.01). MT and PT did not correlate significantly (r=0.29, p>0.1). These findings suggest that the MT does not reflect the excitability of the visual cortex. Regarding excitatory effects, the efficacy of TMS may be different over the motor and visual cortex, likely related to a different excitability of these cortical areas. This should be considered in planning and execution of TMS studies of nonmotor cortical areas.

Brain parenchyma sonography discriminates Parkinson's disease and atypical parkinsonian syndromes.

OBJECTIVE: To study the use of brain parenchyma sonography (BPS) in discriminating between patients with idiopathic PD (IPD) and atypical parkinsonian syndromes (APS). METHODS: Twenty-five patients with APS, 9 with progressive supranuclear palsy (PSP) and 16 with multiple-system atrophy (MSA), and 25 age-matched patients with IPD were prospectively studied with BPS according to a standardized protocol. RESULTS: Twenty-four of the 25 (96%) IPD patients exhibited hyperechogenicity of the substantia nigra (SN) but only 2 of 23 (9%) APS patients (Mann-Whitney U test, p < 0.001). In those two APS patients, SN hyperechogenicity was moderate only, whereas the remaining 21 APS patients had normal SN echogenicity. The specificity of SN hyperechogenicity in detection of clinically diagnosed IPD patients was 96%, and the sensitivity was 91%. If SN hyperechogenicity was marked, APS could be excluded because of a positive predictive value of 100% for IPD. Nucleus lentiformis hyperechogenicity was found in 17 of 22 (77%) APS patients but in only 5 of 22 (23%) IPD patients (Mann-Whitney U test, p < 0.001). Nucleus caudatus and thalamus echogenicity and widths of the third ventricle and of the frontal horns of the lateral ventricles did not discriminate between IPD and APS. Two patients with PSP could not be assessed because of an insufficient bone window. CONCLUSIONS: BPS is a novel and noninvasive method to differentiate highly specifically between IPD and APS. Therefore, BPS might become a standard investigation in parkinsonian disorders.

Normal cerebral hemodynamic response to orthostasis in Parkinson's disease.

In patients with Idiopathic Parkinson's Disease (IPD) without a history of syncope the cardiovascular and cerebrovascular response to orthostatic stress was studied to search for subclinical impairment of autoregulatory mechanisms. Fifteen patients with IPD and 15 healthy age-matched controls were studied at rest and during head-up tilt (HUT). Heart rate, mean arterial blood pressure (MAP) and mean blood flow velocity (MBFV) in the middle cerebral artery were measured simultaneously. Changes of MAP and MBFV and the relationship between both were assessed. During HUT, heart rate increased less in patients than in healthy subjects (16.3% versus 24.2%, p=0.03). In the first minute of orthostasis MAP decreased more in patients than in healthy subjects (-4.0% versus -0.6%, p=0.04). MAP reached the pre-tilt values within 2 min in healthy subjects and 5 min in patients. Cerebral blood flow velocities fell to a similar degree and with similar time characteristics in patients and controls (-15.4% versus -16.7%, p=0.3). In both groups, patients and controls, changes of MAP did not correlate with changes of MBFV. It can be concluded that in IPD patients without symptoms of orthostatic dysregulation the autonomic circulatory control is impaired while the cerebral hemodynamic regulation during orthostasis is unaffected.

Reorganization of human motor cortex after hand replantation.

In 10 patients, reorganizational changes of the motor cortex contralateral to a replanted hand (MCreplant) were studied one to 14 years after complete traumatic amputation and consecutive successful replantation of the hand. The organizational state of MCreplant was assessed for the deafferentated and peripherally deefferentated hand-associated motor cortex and the adjacent motor representation of the proximal arm. For this, response maps were established for the first dorsal interosseus and biceps brachii muscle using focal transcranial magnetic stimulation (TMS) on a skull surface grid. Characteristics of the maps were center of gravity (COG), number of effective stimulation sites, amplitude sum, and amplitudes and response threshold at the optimal stimulation point. The COG is defined by the spatial distribution of response amplitudes on the map and lies over the cortex region with the most excitable corticospinal neurones supplying the recorded muscle. The COG of the biceps map in MCreplant was shifted laterally by 9.8 +/- 3.6 mm (range 5.0-15.7 mm). The extension of the biceps map in MCreplant was increased and the responses were enlarged and had lowered thresholds. For the muscles of the replanted hand, the pattern of reorganization was different: Response amplitudes were enlarged but thresholds, COG, and area of the cortical response map were normal. The different reorganizational phenomena observed for the motor cortical areas supplying the replanted hand and the biceps brachii of the same arm may be influenced by a different extent of deafferentation and by their different role in hand motor control.

Reversible central pontine and extrapontine myelinolysis in a 16-year-old girl.

A rare case of an osmotic demyelination syndrome in a 16-year-old girl is presented. MRI in the acute stage revealed a focal abnormal signal within the basis pontis and both caudate nuclei and putamina. Two years later brain lesions had disappeared on T1- and T2-weighted imaging, indicating that central pontine and extrapontine myelinolysis may be completely reversible.

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.

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.

Influence of transcranial magnetic stimulation on pupil size.

In 22 healthy subjects, painless repetitive transcranial magnetic stimulation (rTMS) was used to investigate the role of the cortex in the regulation of pupil size and the influence of TMS on the central autonomic nervous system. RTMS was performed over three brain regions of each hemisphere (frontal, central, parieto-occipital), over cervical nerve roots and in front of the ear (sham stimulation) while the size of the pupil was measured by infrared oculography. rTMS always elicited a dilatation of both pupils, with its maximum after approximately 1.5 s and without significant R-L difference in latency or amplitude of pupillary response. No differential effects were observed for stimulation over different cortex regions of one hemisphere, but stimulation over the right central region evoked a larger dilatation of the pupil than stimulation over the left. Pupillary dilatation was larger for cervical nerve root stimulation (+13.2+/-8.3% (S.D.) of baseline) than for suprathreshold cortex stimulation (+8.4+/-4.5%, five 10-Hz stimuli). Pupillary dilatation in response to magnetic cortex stimulation appears to reflect a mainly unspecific activation of the sympathetic system rather than an activation of a cortical pupillomotor centre. Sympathetic activation following rTMS of the cortex does not limit its experimental and therapeutic application.

[Magnetic resonance imaging of hemorrhagic transformation in ischemic posterior infarction]. / Kernspintomographische Untersuchung der hämorrhagischen Transformation ischämischer Posteriorinfarkte.

PURPOSE: To describe the incidence, time course, and clinical correlates of hemorrhagic transformation (HT) of ischemic stroke in the posterior cerebral artery territory. METHODS: Within 42 months 48 patients with 52 occipital lobe infarctions were examined by T1- and T2-weighted MR imaging. The extent and distribution of secondary hemorrhage were analysed at different intervals after stroke. Volume of ischemic and hemorrhagic infarction was measured planimetrically. RESULTS: HT was observed in 71% of the infarcts between the 5th day and up to 1 year after stroke. HT was most frequently (88%) observed in the 2nd and 3rd month. HT was present in 55% of small infarcts (< 10 cm3), in 88% of medium size (10-50 cm3), and in all large (> 50 cm3) infarcts. In 92% HT presented with petechial bleedings within the cortex (64%) or less frequently (28%) in subcortical structures. The latter types of HT showed no progression and did not increase the clinical deficits. Space-occupying bleedings occurred in only two large defects. CONCLUSIONS: In ischemic posterior infarction, HT can frequently be detected within the first three months after stroke and is predominantly of the petechial type and seems not to be relevant with regard to clinical deficits.

Cystic lesions of the pineal region--MRI and pathology.

Pineal lesions are rare. Tumours in this location comprise 0.4-1% of intracranial tumours. They grow mainly as solid-mass lesions, and cystic tumours are not common. On MRI, a cystic configuration is associated usually with non-neoplastic pineal lesions rather than with a tumour, but analysis does not allow cystic pineal tumours to be distinguished from glial cysts with certainty. We compared neuroradiological and pathological data from 13 cystic pineal lesions, analysing preoperative MRI. Formalin-fixed, paraffin-embedded surgical specimens were stained routinely and immunocytochemically, using the streptavidin-biotin-complex method. Histology revealed six pineocytomas, four glial cysts, an arachnoid cyst, a low-grade astrocytoma and a teratoma. Signal characteristics of pineocytomas were similar in many respects to those of glial pineal cysts. Histomorphological analysis allowed unambiguous discrimination between pineocytomas and glial pineal cysts.

Changes in cerebral hemodynamics during simple partial motor seizures.

Changes in cerebral perfusion were studied during nine short-lasting simple partial motor seizures (SPS) in an 11-year-old girl. Blood flow velocity changes in both middle cerebral arteries (MCAs) were assessed by transcranial Doppler sonography during simultaneous EEG monitoring. Within 7.4 +/- 1.4 s after electroencephalographic seizure onset, flow velocity in the MCA ipsilateral to the electrical discharges started to increase and then gradually rose up to 70% above baseline values. Spread of the epileptic activity to the other hemisphere in the late stage of seizure was associated with a slight increase in blood flow velocity (<30%) in the contralateral MCA. After the end of the seizure, flow velocities returned to baseline within 47 +/- 7 s. Our findings indicate that focal epileptic seizures evoke asymmetric perfusion increases which are closely related to the onset and cessation of the electroencephalographic seizure activity.

Conduction deficits of callosal fibres in early multiple sclerosis.

OBJECTIVE: To study the diagnostic usefulness of transcallosal inhibition (TI) elicited by transcranial magnetic stimulation (TMS) in detecting central conduction deficits in early multiple sclerosis. Corticospinally mediated excitatory responses evoked by TMS are accepted as a sensitive diagnostic tool in multiple sclerosis. Recently, TI evoked by TMS has been introduced as a new paradigm to test the function of callosal fibres interconnecting both hand associated motor cortices. METHODS: Focal TMS of the motor cortex was performed in 50 patients with early relapsing-remitting multiple sclerosis. Corticospinally mediated (central motor latencies, amplitudes) and transcallosally mediated (onset latency and duration of TI) stimulation effects were investigated. RESULTS: TMS disclosed abnormalities of corticospinally mediated responses in 62% and of TI in 80% of the patients. CONCLUSION: The assessment of TI allows the discovery of lesions within the periventricular white matter that were not accessible by neurophysiological techniques before. This new paradigm increases the sensitivity of TMS with which to detect central conduction deficits in early multiple sclerosis.

CT and MRI in severe hypophosphataemia with central nervous system involvement.

We report a 38-year-old woman with extreme hypophosphataemia in whom CT and MRI disclosed bilateral lesions within the basal ganglia, thalamus and occipital lobes. After adequate substitution of phosphate the lesions grossly resolved and the patient recovered. This case is the first to demonstrate that profound changes of serum phosphate may be associated with reversible brain lesions.

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.

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.