[Central and peripheral deafferent pain: therapy with repetitive transcranial magnetic stimulation]. / Zentrale und periphere Deafferenzierungsschmerzen: Therapie mit der repetitiven transkraniellen Magnetstimulation?

BACKGROUND: This study evaluates the effects of repeated sessions of low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex on central and phantom limb pain. METHODS: Twenty seven patients with central (n=13) and phantom limb (n=14) pain participated in a blind, randomised placebo-controlled study comparing the effect of 1-Hz and 5-Hz rTMS with sham stimulation. Each treatment block consisted of a 5-day baseline phase, a 5-day therapy phase, and an 18-day washout phase. In the therapy phase, 500 stimuli were applied in the particular frequency at about the same time on each day. RESULTS: A reduction in pain immediately after stimulation was observed in all therapy groups. This effect was similar for all treatment conditions, including sham stimulation. No significant long-term effects of rTMS on pain intensity or mood were observed. CONCLUSION: At present, rTMS can not be recommended as a standard therapy for central and phantom limb pain.

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.

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.

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.

In vivo assessment of human visual system connectivity with transcranial electrical stimulation during functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) was used to investigate local and distant cerebral activation induced by transcranial electrical stimulation in order to noninvasively map functional connectivity in the human visual system. Stimulation with lateromedially directed currents and the anode 4.5 cm dorsally to the inion over the right visual cortex induced phosphenes extending into the contralateral lower quadrant of the visual field. fMRI showed a focal hemodynamic response underneath the anode in extrastriate cortex and distant coactivation in subcortical (lateral geniculate nucleus), cortical visual (striate and extrastriate), and visuomotor areas (frontal and supplementary eye fields). This pattern of activation resembles a network of presumably interconnected visual and visuomotor areas. Analysis of activation sites supplies new information about cerebral correlates of phosphenes and shows that the cortical region underneath the cranial stimulation site is not necessarily the origin of behavioral and/or perceptual effects of transcranial stimulation. We conclude that combining transcranial electrical stimulation of neural tissue with simultaneous fMRI offers the possibility to study noninvasively cerebral connectivity in the human brain.

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.

Evaluation of clinical, electrophysiologic, and computed tomographic parameters in replanted hands.

OBJECTIVE: To compare clinical, electrophysiologic, and computed tomography (CT) imaging correlates of reinnervation in replanted limbs. DESIGN: Patients were assessed between 8 and 194 months after replantation of completely severed hands. SETTING: University hospital, departments for neurology and for plastic and reconstructive surgery. PARTICIPANTS: Thirteen patients, 10 with total and 3 with subtotal type V amputation, whose hands had been reattached. INTERVENTIONS: Clinical assessment of function of hand and finger muscles; electromyographic tests of sensory nerve action potentials (SNAPs) of median, ulnar, and radial nerves; and compound motor action potentials (CMAPs) of abductor pollicis brevis, first dorsal interosseus, and abductor digiti minimi muscles. CT assessment of motor unit action potentials. Measurements of both replanted and normal hands. MAIN OUTCOME MEASURES: Medical Research Council scale of force; sensory functions of anatomic areas of nerves; SNAP and CMAP amplitudes; CT area, mean absorption, standard deviation (SD) from mean absorption, and root mean square SD of absorption. RESULTS: Correlates of reinnervation were evidenced by all methods, except by surface recordings of SNAPs, which could not be elicited even in hands with good sensory function. CMAP amplitudes were the electrophysiologic parameter that correlated best with the clinical restoration. Of the CT measures, the cross-sectional area was the most useful parameter for the detection of denervation, but no CT parameter was sufficiently sensitive to detect reinnervation. In cases with good functional recovery, CMAP amplitudes were superior to clinical rating in showing incomplete reinnervation. CONCLUSION: The combination of clinical and electrophysiologic methods supplied sufficient data for a reliable evaluation of reinnervation. Usually, CT parameters did not add useful information.

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.

[The T2-weighted half-Fourier acquired single-shot turbo-spin-echo technic compared to the conventional T2-weighted turbo-spin-echo technic for cerebral magnetic resonance tomography. A sequence comparison]. / Die T2-gewichtete Halb-Fourier Turbo-Spin-Echo-Technik mit erhöhter Echozuglänge im Vergleich zur konventionellen T2-gewichteten Turbo-Spin-Echo-Technik für die zerebrale Magnetresonanztomographie. Ein Sequenzvergleich.

PURPOSE: To compare a T2-weighted half-fourier acquired single-shot turbo spin-echo (HF-TSE) sequence (HA-STE-sequence) for cerebral MRI with a standard T2-weighted fast spin-echo (TSE) sequence. MATERIALS AND METHODS: Signal-to-noise (SNR) and contrast-to-noise ratios (CNR) for different cerebral structures, and intracerebral lesions as well as the detectability of intracerebral lesions depending on size and relaxation properties were evaluated on cranial MR examinations of 46 patients with both a TSE and a HF-TSE sequence. RESULTS: SNR and CNR were found to be significantly higher with the TSE sequence for all normal structures and lesions except CSF, and lesions with short relaxation time T2 (p < 0.001). The number of detected lesions larger than 10 mm was similar with both sequences. Thirty-six (TSE) and 34 (HF-TSE) hyperintense, and 7 (TSE) and 2 (HF-TSE) hypointense lesions of at least 5 mm but less than 10 mm in size were detected. Thirty-three (TSE) and 10 (HF-TSE) hyperintense, and 2 (TSE) and no (HF-TSE) hypointense lesions smaller than 5 mm were detected. CONCLUSION: Due to its short acquisition time, the HF-TSE sequence is an alternative for MR examinations of non-compliant or claustrophobic patients. The low SNR and CNR relative to the TSE-technique are limiting factors as to the detectability of small lesions or lesions with low contrast to surrounding structures, with the risk of an increasing number of false negative results in lesions with short T2 relaxation time smaller than 10 mm.

[Variant of Klippel-Trenaunay syndrome. A case report]. / Variante eines Klippel-Trenaunay-Syndroms--ein Fallbericht.

Klippel-Trenaunay-Syndrome is a rare congenital vascular malformation with cutaneous naevi, varicose veins and limb hypertrophy. We report a patient with a variant of this syndrome presenting with extensive varicose veins and arteriovenous shunts within the left arm, bony hypotrophy of the left hand, mucocutaneous melanin spots in the face and thrombocytopenia. Imaging techniques play a major role in making a diagnosis in angiophakomatoses.

[Reversible cyclosporin A-induced leukoencephalopathy: a case report and differential diagnosis discussion]. / Reversible Cyclosporin-A-induzierte Leukenzephalopathie--Fallbeschreibung und differential-diagnostische Uberlegungen.

The pathogenesis of Cyclosporin A (CsA) induced toxic leukoencephalopathy is unclear. CCT and CMRI reveal hypodense respectively hyperintense bilateral and symmetrical changes predominantly in the posterior white matter. We report a patient with a severe CsA induced toxic leukoencephalopathy in whom clinical symptoms (complete loss of brainstem functions, coma) and morphological changes in CCT and CMRI were completely reversible after immunosuppression with CsA has been stopped. We furthermore discuss the differential diagnoses of CCT and CMRI findings.

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.

CSF flow studies of intracranial cysts and cyst-like lesions achieved using reversed fast imaging with steady-state precession MR sequences.

BACKGROUND AND PURPOSE: Differentiating between intracranial cysts or cyst-like structures and communicating or noncommunicating cysts is often not possible with cranial CT or nonfunctional MR imaging. We evaluated a retrospective ECG-gated fast imaging with steady-state precession (PSIF) MR sequence with optional cine mode to differentiate cystic masses from enlarged CSF spaces and to determine the accuracy of detecting communication between cysts and neighboring CSF spaces. METHODS: Fourteen patients with intracranial cystic masses underwent CSF flow studies with an ungated and a retrospective ECG-gated cine-mode PSIF sequence in addition to spin-echo imaging. Findings were evaluated retrospectively by using a five-point rating scale and without knowledge of clinical or other imaging findings. Results were compared with intraoperative findings or with results of intrathecal contrast studies. RESULTS: Eighteen arachnoid cysts and one enlarged cisterna magna were diagnosed. Improved differentiation between cysts and enlarged CSF spaces was obtained with cine-mode PSIF imaging in six lesions (six patients). Increased diagnostic certainty as to communication between cysts and CSF spaces was obtained in 18 cysts (13 patients). Diagnoses were verified by membranectomy in five lesions, by CT cisternography in five lesions, and indirectly by shunting in one cystic lesion. In one case, MR diagnosis was not confirmed by CT cisternography. CONCLUSION: Cine-mode MR imaging with a retrospective ECG-gated flow-sensitive PSIF sequence contributed to the certainty of communication between arachnoid cysts and neighboring CSF spaces with an accuracy of 90%, using surgical findings or intrathecal contrast studies as reference. Differentiation between intracranial cysts and enlargement of CSF spaces and other cystic masses was improved in 25% of cases.

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.

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.

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.

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.

Magnetic stimulation over different brain regions: no differential effects on the elicited sympathetic skin responses.

Peak latencies and amplitudes of sympathetic skin responses (SSRs) of the hand following magnetic stimulation at different sites with two or five consecutive 10-Hz stimuli were investigated with regard to safety aspects of repetitive transcranial magnetic cortex stimulation (rTMS). The amount of sympathetic activation as assessed by the amplitudes of the SSRs depended on the stimulation site and decreased in the following order: brachial plexus stimulation > nerve root stimulation > stimulation over the brain > activation by acoustic coil artefact. When stimulating over six different regions of the cortex (frontal, central, parieto-occipital, and both hemispheres), the elicited SSRs had similar amplitudes and peak latencies. The SSRs elicited by rTMS over the motor cortex were not related to the sum of the amplitudes of excitatory muscle compound responses. Currents with opposite directions over the motor cortex markedly influenced the size of the motor responses but not of the SSRs. The number of consecutive 10-Hz stimuli did not influence the latencies or amplitudes of the SSRs. It can be concluded that SSRs after magnetic stimulation over peripheral nerves or the brain are a correlate of an unspecific arousal reaction. A therapeutic application of short series of rTMS should not be limited by the amount of sympathetic activation.