Kai M. Rösler

The clinical diagnostic utility of transcranial magnetic stimulation: Report of an IFCN committee

The review focuses on the clinical diagnostic utility of transcranial magnetic stimulation (TMS). The central motor conduction time (CMCT) is a sensitive method to detect myelopathy and abnormalities may be detected in the absence of radiological changes. CMCT may also detect upper motor neuron involvement in amyotrophic lateral sclerosis. The diagnostic sensitivity may be increased by using the triple stimulation technique (TST), by combining several parameters such as CMCT, motor threshold and silent period, or by studying multiple muscles. In peripheral facial nerve palsies, TMS may be used to localize the site of nerve dysfunction and clarify the etiology. TMS measures also have high sensitivity in detecting lesions in multiple sclerosis and abnormalities in CMCT or TST may correlate with motor impairment and disability. Cerebellar stimulation may detect lesions in the cerebellum or the cerebellar output pathway. TMS may detect upper motor neuron involvement in patients with atypical parkinsonism and equivocal signs. The ipsilateral silent period that measures transcallosal inhibition is a potential method to distinguish between different parkinsonian syndromes. Short latency afferent inhibition (SAI), which is related to central cholinergic transmission, is reduced in Alzheimers disease. Changes in SAI following administration of cholinesterase inhibitor may be related to the long-term efficacy of this treatment. The results of MEP measurement in the first week after stroke correlate with functional outcome. We conclude that TMS measures have demonstrated diagnostic utility in myelopathy, amyotrophic lateral sclerosis and multiple sclerosis. TMS measures have potential clinical utility in cerebellar disease, dementia, facial nerve disorders, movement disorders, stroke, epilepsy, migraine and chronic pain.

Effort-induced mirror movements: A study of transcallosal inhibition in humans

During sustained, fatiguing maximal voluntary contraction of muscles of one hand, muscles of the other hand gradually become activated also. Such effort-induced mirror movements indicate a decreased ability of the central nervous system (CNS) to selectively control individual muscles. We studied whether altered transcallosal inhibition (TCI) contributed to this phenomenon. TCI was determined in ten healthy subjects by measuring the ipsilateral silent period (iSP) and the contralateral silent period (cSP) during a sustained contraction of the abductor digiti minimi, induced by focal unihemispheric ipsilateral transcranial magnetic stimulation. Mirror movements occurred in all subjects in response to the effort. There was a bilateral increase in cSPs and a parallel increase in the iSP in the contralateral working muscle. In contrast, the iSP in the mirroring muscle remained unchanged, explained by a balance of increased crossed pyramidal inhibition (cSP) and decreased transcallosal inhibition. In finely tuned unimanual movements, mirroring activity of the contralateral hand is suppressed by TCI originating in the working hemisphere. During sustained, effortful contractions, the outflow of the contralateral hemisphere is increased due to reduced TCI. Effort-induced mirror contractions are thus the result of disinhibition of contralateral crossed projections rather than disinhibition of ipsilateral uncrossed pathways.

Diagnostic value of paraclinical tests in multiple sclerosis: relative sensitivities and specificities for reclassification according to the Poser committee criteria.

The yield of paraclinical tests was evaluated in a prospective study of 189 consecutive patients referred for suspected multiple sclerosis (142 patients with multiple sclerosis, 47 non-multiple sclerosis patients on discharge). Patients were first classified according to the Poser criteria by the clinical findings. Subsequently, the results of paraclinical tests (cranial MRI, visually evoked potentials (VEPs), somatosensory evoked potentials by tibial nerve stimulation (SSEPs), motor evoked potentials (MEPs), and analysis of CSF for oligoclonal banding and IgG-index (CSF)) were taken into account. The percentage of reclassified patients (reclassification sensitivity, RS) was always lower than the percentage of abnormal results (diagnostic sensitivity, DS), and the divergence of RS v DS differed between the tests (60% v 84% in MRI, 31% v 77% in CSF, 29% v 37% in VEPs, 20% v 68% in MEPs, and 12% v 46% in SSEPs respectively). False reclassifications of non-multiple sclerosis patients to multiple sclerosis would have occurred with all tests (MRI: six of 47 patients, (reclassification specificity 88%); CSF: one (98%); VEPs: two (96%); MEPs: two (96%); SSEPs: four (91%); P < 0.05). Although MRI had superior diagnostic capacity, 57 of the 142 patients with multiple sclerosis were not reclassified by the MRI result, 12 of whom were reclassified by CSF and 18 by one of the evoked potential (EP) studies. Of the 98 patients not reclassified by CSF, 53 were reclassified by MRI and 39 by EPs. The results suggest that for the evaluation of paraclinical tests in suspected multiple sclerosis, comparison of diagnostic sensitivities is inappropriate. In general, a cranial MRI contributes most to the diagnosis; however, due to its comparatively low specificity and its considerable number of negative results, EP or CSF studies are often useful to establish the diagnosis of multiple sclerosis.

Quantification of upper motor neuron loss in amyotrophic lateral sclerosis

OBJECTIVE To quantitatively estimate upper motor neuron (UMN) loss in ALS. METHODS We used the recently developed triple stimulation technique (TST) to study corticospinal conduction to 86 abductor digiti minimi muscles of 48 ALS patients. This method employs a collision technique to estimate the proportion of motor units activated by a transcranial magnetic stimulus. At the same time, it yields an estimate of lower motor neuron (LMN) integrity. RESULTS The TST disclosed and quantified central conduction failures attributable to UMN loss in 38 sides of 24 patients (subclinical in 15 sides), whereas conventional motor evoked potentials detected abnormalities in only 18 sides of 12 patients (subclinical in two sides). The increased sensitivity of the TST to detect UMN dysfunction was particularly observed in early cases. Increased central motor conduction times (CMCT) occurred exclusively in sides with conduction failure. In sides with clinical UMN syndromes, the TST response size (but not the CMCT) correlated with the muscle weakness. In sides with clinical LMN syndromes, the size of the peripherally evoked compound muscle action potentials correlated with the muscle weakness. CONCLUSION The TST is a sensitive method to detect UMN dysfunction in ALS. It allows a quantitative estimate of the UMN loss, which is related to the functional deficit. Therefore, the TST has a considerable impact on diagnostic certainty in many patients. It will be suited to follow the disease progression and therapeutic trials.

Electrophysiological characteristics of lesions in facial palsies of different etiologies. A study using electrical and magnetic stimulation techniques.

Using magnetic stimulation techniques in addition to conventional electrical stimulation, the entire facial motor pathway can be assessed electrophysiologically. To study the diagnostic yield of these examinations, 174 patients with facial palsies of a variety of etiologies were examined (85 Bells palsies, 24 Guillain-Barré syndrome (GBS), 19 Lyme borreliosis, 17 zoster oticus, 12 meningeal affections, 10 brain-stem disorders and 7 HIV-related facial palsies). The facial nerve was stimulated electrically at the stylomastoid fossa and magnetically within its canalicular portion. Additionally, the face-associated contralateral motor cortex was stimulated magnetically. Recordings were from the nasalis or mentalis muscle, or both, using surface electrodes. Bells palsy patients showed typically a unilateral local hypoexcitability of the facial nerve to canalicular stimulation. In GBS, bilateral latency prolongations were frequent, as expected for a myelinic disorder. In contrast, in zoster, predominant axonotmesis was unilateral, and in HIV infection sometimes bilateral. The method was very sensitive to detect subclinical dysfunctions in meningo-radiculitis and malignant meningeal diseases, either prior to the onset of palsy, or on the contralateral (clinically unaffected) side. It also distinguished reliably between central and peripheral facial motor pathway lesions. In our experience, these inexpensive and non-invasive electrophysiological techniques contribute substantially to the differential diagnosis of facial palsies.

Quantification of Uhthoff's phenomenon in multiple sclerosis: a magnetic stimulation study

OBJECTIVE To quantify temperature induced changes (=Uhthoff phenomenon) in central motor conduction and their relation to clinical motor deficits in 20 multiple sclerosis (MS) patients. METHODS Self-assessment of vulnerability to temperature and clinical examination were performed. We used motor evoked potentials to measure central motor conduction time (CMCT) and applied the triple stimulation technique (TST) to assess conduction failure. The TST allows an accurate quantification of the proportion of conducting central motor neurons, expressed by the TST amplitude ratio (TST-AR). RESULTS Temperature induced changes of TST-AR were significantly more marked in patients with prolonged CMCT (P=0.037). There was a significant linear correlation between changes of TST-AR and walking velocity (P=0.0002). Relationships were found between pronounced subjective vulnerability to temperature and (i) abnormal CMCT (P=0.02), (ii) temperature induced changes in TST-AR (P=0.04) and (iii) temperature induced changes in walking velocity (P=0.04). CMCT remained virtually unchanged by temperature modification. CONCLUSIONS Uhthoff phenomena in the motor system are due to varying degrees of conduction block and associated with prolonged CMCT. In contrast to conduction block, CMCT is not importantly affected by temperature. SIGNIFICANCE This is the first study quantifying the Uhthoff phenomenon in the pyramidal tract of MS patients. The results suggest that patients with central conduction slowing are particularly vulnerable to develop temperature-dependent central motor conduction blocks.

Effect of discharge desynchronization on the size of motor evoked potentials: an analysis

OBJECTIVE Motor evoked potentials (MEPs) after transcranial magnetic brain stimulation (TMS) are smaller than CMAPs after peripheral nerve stimulation, because desynchronization of the TMS-induced motor neurone discharges occurs (i.e. MEP desynchronization). This desynchronization effect can be eliminated by use of the triple stimulation technique (TST; Brain 121 (1998) 437). The objective of this paper is to study the effect of discharge desynchronization on MEPs by comparing the size of MEP and TST responses. METHODS MEP and TST responses were obtained in 10 healthy subjects during isometric contractions of the abductor digiti minimi, during voluntary background contractions between 0% and 20% of maximal force, and using 3 different stimulus intensities. Additional data from other normals and from multiple sclerosis (MS) patients were obtained from previous studies. RESULTS MEPs were smaller than TST responses in all subjects and under all stimulating conditions, confirming the marked influence of desynchronization on MEPs. There was a linear relation between the amplitudes of MEPs vs. TST responses, independent of the degree of voluntary contraction and stimulus intensity. The slope of the regression equation was 0.66 on average, indicating that desynchronization reduced the MEP amplitude on average by one third, with marked inter-individual variations. A similar average proportion was found in MS patients. CONCLUSIONS The MEP size reduction induced by desynchronization is not influenced by the intensity of TMS and by the level of facilitatory voluntary background contractions. It is similar in healthy subjects and in MS patients, in whom increased desynchronization of central conduction was previously suggested to occur. Thus, the MEP size reduction observed may not parallel the actual amount of desynchronization.

Trial-to-trial size variability of motor-evoked potentials. A study using the triple stimulation technique

Motor-evoked potentials (MEPs) vary in size from one stimulus to the next. The objective of this study was to determine the cause and source of trial-to-trial MEP size variability. In two experiments involving 10 and 14 subjects, the variability of MEPs to cortical stimulation (cortical-MEPs) in abductor digiti minimi (ADM) and abductor hallucis (AH) was compared to those responses obtained using the triple stimulation technique (cortical-TST). The TST eliminates the effects of motor neuron (MN) response desynchronization and of repetitive MN discharges. Submaximal stimuli were used in both techniques. In six subjects, cortical-MEP variability was compared to that of brainstem-MEP and brainstem-TST. Variability was greater for MEPs than that for TST responses, by approximately one-third. The variability was the same for cortical- and brainstem-MEPs and was similar in ADM and AH. Variability concerned at least 10–15% of the MN pool innervating the target muscle. With the stimulation parameters used, repetitive MN discharges did not influence variability. For submaximal stimuli, approximately two-third of the observed MEP size variability is caused by the variable number of recruited alpha-MNs and approximately one-third by changing synchronization of MN discharges. The source of variability is most likely localized at the spinal segmental level.

Task-dependent facilitation of motor evoked potentials during dynamic and steady muscle contractions

Task‐dependent differences in the facilitation of motor evoked potentials (MEPs) following cortex stimulation were studied in a proximal (deltoid) and a distal muscle (abductor digiti minimi; ADM) in 23 healthy subjects during both dynamic and steady contractions of the target muscle under isometric and under nonisometric conditions. In the deltoid, MEP amplitudes were significantly greater if stimulation was performed during dynamic contractions than during steady contractions, despite equal background electromyographic levels just prior to the stimulus. The same task‐specific extra facilitation of deltoid MEP amplitudes was also found with magnetic stimulation of the brain stem instead of the cortex in 3 subjects. In the ADM, no such task‐dependent extra facilitation of MEPs during dynamic contractions was found. It is concluded that in the deltoid, during dynamic contractions, a greater proportion of the spinal motoneurons is close to depolarization threshold (greater “subliminal fringe”) whereas the number of firing motoneurons is similar to that during steady contraction. The lack of task‐dependent extra facilitation of MEPs in the ADM is explained by the predominant recruitment principle for force gradation in small hand muscles, which is in contrast to the predominant frequency principle used in proximal muscles.

Amyotrophic lateral sclerosis versus cervical spondylotic myelopathy: a study using transcranial magnetic stimulation with recordings from the trapezius and limb muscles

OBJECTIVE We report an electrophysiological method to differentiate amyotrophic lateral sclerosis (ALS) from cervical spondylotic myelopathy (CSM). METHODS Motor evoked potentials (MEPs) by transcranial magnetic stimulation were investigated in patients with ALS (n=10) and CSM (n=9). In addition to limb MEPs using the triple stimulation technique (TST) at upper limbs, MEPs recorded from trapezius muscles were compared with those obtained from 23 normal subjects. The parameters studied were: central motor conduction time, amplitude ratio and, for the trapezius, the interside asymmetry. RESULTS Whereas limb MEPs were abnormal in most ALS and CSM patients (17/19), trapezius MEPs were abnormal in all ALS patients, and normal in 8 out of 9 CSM patients. CONCLUSION Recording of trapezius MEPs is a valuable addition to the limb MEPs study, since it distinguishes ALS from SCM in most patients.