[supplements to clinical neurophysiology] transcranial magnetic stimulation and transcranial direct...

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Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation (Supplements to Clinical Neurophysiology, Vol. 56) Editors: W. Paulus, F. Tergau, M.A. Nitsche, le. Rothwell, U. Ziemann, M. Hallett © 2003 Elsevier Science B.V. All rights reserved Chapter 35 Transcranial magnetic stimulation in brainstem lesions and lesions of the cranial nerves Peter P. Urban Department of Neurology, University of Mainz; Langenbeckstr. 1, D-55IOI Mainz (Germany) 341 1. Introduction Transcranial magnetic stimulation (TMS) represents a non-invasive, safe, and painless method of motor cortex activation for the functional assessment of the rapid conducting corticobulbar and corticospinal projections. TMS delivered to different levels of the motor system can provide information on the excitability of the motor cortex, the functional integrity of intracortical neuronal structures, the conduction along corticospinal, corticonuclear, and callosal fibres, as well as on the function of nerve roots and the peripheral motor pathway to the muscles. Brain stem lesions may lead to corticonu- clear and/or corticospinal tract involvement. It is therefore useful to examine both tracts, which can be identified following the accurate selection of the respective recording and stimulation site. The focus of this chapter is not only on TMS applications in brainstem pathology, but also on the description of TMS techniques for the evaluation of motor cranial nerve function, which is an essential * Correspondence to: Dr. Peter P. Urban, Department of Neurology, University of Mainz, Langenbeckstr. I, 0-55101 Mainz, Germany. Tel.: +49-6131-175162, Fax: +49-6131-173271; E-mail: [email protected] measure in the diagnostic workup of brainstern lesions. Applications of TMS to the cranial nerve innervated muscles have been the objective of numerous investigations, ranging from basic neu- roanatomic studies to determine the central course of corticonuclear projections to clinical applications carried out to determine the location of lesions, investigate the pathophysiology of ischemic dysarthria, detect clinically silent lesions in multiple sclerosis, obtain prognostic information regarding persistent motor deficits following cerebral ischemia, and to identify corticonuclear tract involvement in motor neuron diseases. TMS is also of clinical relevance in the evaluation of those peripheral cranial nerve lesions which most frequently affect the facial nerve. 2. Methods Brainstem lesions may affect the corticospinal and/or corticobulbar projections. A description of the stimulation and recording technique from the limbs is given in the IFeN recommendations (Rossini et al., 1994; Rothwell et al., 1999), as well as by a number of recently published reviews (Rossini and Rossi, 1998; Weber and Eisen, 2002; Kobayashi and Pascual-Leone, 2(03). In contrast to their application

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Page 1: [Supplements to Clinical Neurophysiology] Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation, Proceedings of the 2nd International Transcranial Magnetic

Transcranial Magnetic Stimulation and Transcranial DirectCurrent Stimulation (Supplements to Clinical Neurophysiology, Vol. 56)Editors: W. Paulus, F. Tergau, M.A. Nitsche, le. Rothwell, U. Ziemann, M. Hallett© 2003 Elsevier Science B.V. All rights reserved

Chapter 35

Transcranial magnetic stimulation in brainstem lesions andlesions of the cranial nerves

Peter P. Urban

Department of Neurology, University of Mainz; Langenbeckstr. 1, D-55IOI Mainz (Germany)

341

1. Introduction

Transcranial magnetic stimulation (TMS) representsa non-invasive, safe, and painless method of motorcortex activation for the functional assessment of therapid conducting corticobulbar and corticospinalprojections. TMS delivered to different levels of themotor system can provide information on theexcitability of the motor cortex, the functionalintegrity of intracortical neuronal structures, theconduction along corticospinal, corticonuclear, andcallosal fibres, as well as on the function of nerveroots and the peripheral motor pathway to themuscles. Brain stem lesions may lead to corticonu-clear and/or corticospinal tract involvement. It istherefore useful to examine both tracts, which can beidentified following the accurate selection of therespective recording and stimulation site.

The focus of this chapter is not only on TMSapplications in brainstem pathology, but also on thedescription of TMS techniques for the evaluation ofmotor cranial nerve function, which is an essential

* Correspondence to: Dr. Peter P. Urban, Departmentof Neurology, University of Mainz, Langenbeckstr. I,0-55101 Mainz, Germany.Tel.: +49-6131-175162, Fax: +49-6131-173271;E-mail: [email protected]

measure in the diagnostic workup of brainsternlesions. Applications of TMS to the cranial nerveinnervated muscles have been the objective ofnumerous investigations, ranging from basic neu-roanatomic studies to determine the central course ofcorticonuclear projections to clinical applicationscarried out to determine the location of lesions,investigate the pathophysiology of ischemicdysarthria, detect clinically silent lesions in multiplesclerosis, obtain prognostic information regardingpersistent motor deficits following cerebral ischemia,and to identify corticonuclear tract involvement inmotor neuron diseases. TMS is also of clinicalrelevance in the evaluation of those peripheral cranialnerve lesions which most frequently affect the facialnerve.

2. Methods

Brainstem lesions may affect the corticospinal and/orcorticobulbar projections. A description of thestimulation and recording technique from the limbsis given in the IFeN recommendations (Rossiniet al., 1994; Rothwell et al., 1999), as well as by anumber of recently published reviews (Rossini andRossi, 1998; Weber and Eisen, 2002; Kobayashi andPascual-Leone, 2(03). In contrast to their application

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in limb muscles, fractionated examinations of theprojections to the cranial nerve muscles are lesscommonly performed, and frequently require specialrecording and stimulation techniques, which aredescribed in greater detail in this review. Recordingsfrom the facial muscles and the tongue areparticularly useful in the assessment of corticonuclearfunction due to the relatively large size of the corticalrepresentation area of these structures.

3. Masticatory muscles (N. V)

Motor evoked potentials (MEP) of the masticatorymuscles by TMS have been described for healthysubjects and patients with hemiplegia, trigeminalneuralgia, amyotrophic lateral sclerosis (ALS), andmultiple sclerosis (e.g. Cruccu et al., 1989; TUrket al., 1994; Trompetto, 1998). However, reliablerecordings of TMS evoked MEPs of the massetermuscle are more difficult to achieve than those ofthe facial, tongue or intrinsic hand muscles dueto methodological problems associated with therecording and stimulation technique.

3.1. Recording technique

Recordings from the masseter muscle are performedmost frequently, although recordings from othermasticatory muscles as, e.g. the anterior digastricmuscle (Gooden et al., 1999), and the medial pterygoidmuscle (TUrk et al., 1994) have been reported. Arelevant methodological problem is the presence ofvolume conducted potentials from the overlying facialmuscles which are also activated in the course ofcortical stimulation. To avoid recording of volumeconducted facial muscle activity, both an enoralrecording technique (Turk et al., 1994) and a veryshort distance between active and reference electrodeshave been recommended (Guggisberg et al., 2(01).Furthermore, selective preactivation of the mastica-tory muscles is required to focus on the target muscleand to reduce the relative influence of the relaxedneighboring muscles.

3.2. Stimulation technique

3.2.1. Stimulation of the motor cortexDue to the relatively small cortical representation areafor masticatory muscles, the correct placement of themagnetic coil is essential (Guggisberg et al., 2001).Themasticatory muscles also have a higher motor thresholdcompared to facial muscles and the tongue. This maybe accounted for by the presence of fewer corticalconnections to the pyramidal cells (Guggisberg et al.,2(01). The location of the optimal stimulation siteusing a circular coil, has been described as 2-4 emparamedially to the vertex (TUrk et al., 1994). For thefigure-of-eight coil, a coil orientation of 1200 relative toa fronto-dorsal line in an area 4-10 em lateral to thevertex and 0-4 em frontal to the bi-auricular line hasbeen shown to have the lowest motor threshold, thehighest amplitudes, and shortest MEP latencies fromthe masseter muscle (Guggisberg et al., 2(01).

3.2.2. Peripheral nerve stimulationThe proximal part of the trigeminal motor nerve can beactivated with an ipsilateral coil position 6 em lateral tothe vertex. The responses occur at a mean latency ofabout 2 ms (Cruecu et al., 1989; Guggisberg et al.,2(01). Comparing the responses of direct electricaltrigeminal nerve stimulation during microvasculardecompression operations with TMS evoked responsespreoperatively, it has been shown that TMS activatesthe trigeminal nerve distal to the root entry zone withinthe cerebrospinal fluid near the porus trigerninale.However, the activation site was not constant andmigrated distally at increasing stimulus intensities(Schmid et al., 1995). Electrical stimulation of thedistal trigeminal nerve at the zygomatic arch evokesperipheral compound muscle action potentials(CMAP) with a latency of about 1.5 ms. However, dueto the small distance between stimulation and recordingsite, the presence of a substantial stimulus artefact ofteninterferes with the determination of the CMAP onset.

4. Facial muscles (N. Vll)

Recordings from the facial muscles allow reliableconduction measurements across the central and

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peripheral motor pathways. Clinical applicationsinclude supranuclear and infranuclear facial palsiesof different etiologies, and the detection of aclinically silent involvement of the supranuclear tractin multiple sclerosis and ALS.

4.1. Recording technique

There are no firm recommendations regarding therecording site, and CMAPs have been recorded fromthe nasalis, mentalis, orbicularis oculi, frontalis,triangularis, levator labii, and buccinator muscles. Asystematic comparison of these recording sites as tothe elicitation of a CMAP, stimulus artefact,interferences with the Rl-component of the blinkreflex, cross-talk from the contralateral face, intersidedifferences of the amplitudes and intraindividualreproducibility showed clear advantages for thebuccinator and triangularis muscles under facial nervestimulation, and for the buccinator and levator labiimuscles under motor cortex stimulation (Urban et al.,2oo2a). These findings are consistent with results ofrecently published neuroanatomic studies demon-strating that only the lateral facial nucleus, whichcontains neurons for the orofacial muscles, receivescontralateral projections from the contralateralprimary motor cortex, while the upper face musclesreceive projections from the supplementary motorcortex and rostral parts of the gyrus cinguli(Morecraft et al., 2001). Thus, the orofacial musclesare especially suitable for the evaluation of the centralfacial motor pathway.

We prefer the use of an enoral technique forrecordings from the buccinator muscle, because it ischaracterized by a high CMAP amplitude caused bythe large muscle volume, no volume conduction fromthe contralateral side as a result of the lateral position,no relevant stimulus artefact associated with theenoral recording technique, no Rl-component of theblink reflex resulting from the caudal position, and adistinct negative deflection of the CMAP due to theclearly defined nerve entry zone (motor point). Forthis purpose, pairs of AglAgCI-surface disc elec-trodes are embedded at a distance of 18 mm in aspecially designed fork-shaped metacrylate device

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adapted to the oral vestibulum (Urban et al., 1997a).The electrodes are in contact with the insides of thecheeks and a slight contraction of the buccinatormuscles during motor cortex stimulation is achievedby pursing the lips.

4.2. Stimulation technique

4.2.1. Stimulation of the motor cortexThe center of a circular coil is positioned tangentially2-4 em (buccinator muscle) lateral of Cz for motorcortex stimulation. Using a figure-of-eight coil, themost effective site for stimulation has been describedas 8-10 em lateral to the vertex, with a coil orienta-tion allowing the current induced into the brain toflow in a posterior to anterior direction (Meyer et al.,1994). Stimulation intensity is increased stepwiseduring slight preactivation until stable latencies (totalmotor conduction time: TMCT) are achieved.Recording of volume-conducted activity from theadjacent masticatory muscles is negligible due to theirhigher motor threshold, as may be observed in thepresence of absent activity in complete peripheralfacial palsy.

4.2.2. Peripheral nerve stimulationThe proximal peripheral facial nerve is stimulatedmagnetically at the extra-axial intracranial segment.A comparison of the responses to direct electricalfacial nerve stimulation during microvascular decom-pression operations with preoperatively recordedTMS findings showed that TMS activates the facialnerve at the end of the labyrinthine segment (canalic-ular stimulation) on leaving the low-resistancecerebrospinal fluid and entering the high resistancepetrous bone (Schmid et al., 1991). To achieveexcitation of the proximal facial nerve, the circularcoil is placed in a parieto-occipital position ipsilat-erally to the facial nerve. For stimulation of the left(right) peripheral nerve, side "B" ("A") of the circularcoil is viewed from the outside. The peripheralmotor conduction time (PMCT) is about 5 msand serves to calculate the central motor conductiontime (CMCT) (TMCT - PMCT =CMCT). Only arelatively low stimulation intensity (about 30-50%

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of the maximal stimulator output) should be appliedfor magnetic stimulation to avoid stimulation of thedistal nerve at the stylomastoid foramen. Inadvertentfacial nerve stimulation at the stylomastoid foramencan be identified by comparing the PMCT with thedistal motor latency (DML), which is equal tothe conduction time on electrical stimulation of thedistal facial nerve at the stylomastoid foramen.The normal value for the difference between PMCTand DML (i.e. the transosseal conduction time)is about 1-1.5 ms (Rosler et al., 1989; Urbanet al., 1997a), although it is lower in the presenceof inadvertent distal nerve stimulation. In the lattercase, the stimulation intensity should be reducedand the coil position ought to be moved to a moreparietal site.

4.2.3. InterpretationBecause stimulation of the motor cortex yieldsvarying ipsilateral responses in healthy subjects, onlythe contralateral responses should be considered(Urban et al., I997a). A supranuclear lesion of thecorticofacial pathways is assumed, when: (1) noresponses are obtained on motor cortex stimulation(no reproducible response at four consecutive trialswith a gain of 200 (V/div); (2) the amplitudecorrelation between motor cortex response andM-wave amplitude with electrical stimulation is (10%(MEPIM-wave-ratio); and (3) a delayed CMCT orinterside difference of the CMCT (> 2.5 SD from thenormal mean) is present. An infranuclear facial nervelesion may be assumed when the interside amplitudedifference of the M-wave is (50% compared to thenormal side) 10 days after the acute lesion.

5. Sternocleidomastoid muscle and trapeziusmuscle (N. XI)

A clinical application of motor evoked potentials(MEP) of the sternocleidomastoid (SCM) andtrapezius muscles evoked by TMS has recently beendescribed for the differentiation of amyotrophiclateral sclerosis and cervical spondylotic myelopathy(Truffert et al., 2000).

5.1. Recording technique

Recordings from both the sternocleidomastoid andtrapezius muscles have been reported in the literature.However, using surface electrode recordings, addi-tional volume conducted activity from the overlyingplatysma (SCM) (Thompson et aI., 1997), and theunderlying neck muscle activity (trapezius muscle)(Berardelli et al., 1991) has to be considered duringmotor cortex stimulation.

5.2. Stimulation technique

5.2.1. Stimulation of the motor cortexThe results of a number of studies using magneticand electric transcranial stimulation (Gandevia andApplegate, 1988; Berardelli et al., 1991; Odergrenand Rimpilainen, 1996; Thompson et al., 1997;Strenge and Jahns, 1998), and clinical observationsduring hemispheric suppression of one hemisphereby amytal during the Wada test (DeToledo and Dow,1998) have shown that stimulation of the motorcortex evokes both bilateral, but predominantlycontralateral responses in the SCM and trapeziusmuscle. The center of a circular coil is positionedtangentially 3-4 em lateral of Cz and 1-2 cm anteriorto the interaural line for motor cortex stimulation.Mapping studies using a figure-of-eight coil formotor cortex stimulation and dual monopolarshielded needles for muscle activity recordingsdemonstrated that the SCM is represented at thecerebral convexity medial to the upper limb repre-sentation, leading to short latency (mean 2.2 ms)responses in the contralateral SCM and longer latency(mean 9.3 rns) responses in the ipislateral SCM(Thompson et al., 1997).

5.2.2. Peripheral nerve stimulationThe accessory nerve may be magnetically stimulatedby placing the centre of the coil below the mastoid(Priori et al., 1991). No comparative intraoperativeand preoperative studies on the most suitablestimulation site have been publisheded thus far. Thedistal accessory nerve is generally stimulated electri-cally at the midpoint of the posterior border of the

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SCM, and the CMAP is recorded from the trapeziusmuscle (e.g. Petrera and Trojaborg, 1984).

6. Tongue muscles (N. xm

Recordings from the tongue enable reliable conduc-tion measurements across the central and peripheralmotor pathways. Clinical applications include theidentification of supranuclear lesions of the corticol-ingual pathway of different etiologies in dysarthria,and the detection of clinically silent corticonucleartract involvement in multiple sclerosis and ALS.

6.1. Recording technique

Non-invasive recordings from the genioglossusmuscle can be performed reliably with an enoralsurface electrode technique. For this purpose, pairsof Ag/AgCl-surface disc electrodes are embedded ata distance of 18 mm in a specially designed spoon-shaped metacrylate device, which is adapted to theoral vestibulum (Urban et al., 1994, 1996, 1997c;Muellbacher et al., 1994). The electrodes are incontact with the surface of the tongue, and slightcontraction of the genioglossus during motor cortexstimulation is achieved by pressing the device gentlyagainst the hard palate.

6.2. Stimulation technique

6.2.1. Stimulation of the motor cortexThe centre of a circular coil is positioned tangentially4-6 em lateral of Cz for motor cortex stimulation.The optimal reported stimulation site using a focal8-shaped coil (outside diameter of one half-coil:8.5 em) is 8-10 ern lateral to the midline, and 2-4 ernanterior to the interaural line (Meyer et al. 1997).Stimulation strength is increased stepwise duringslight preactivation until stable latencies (total motorconduction time: TMCT) are achieved.

6.2.2. Peripheral nerve stimulationMagnetic stimulation is assumed to activate thehypoglossal nerve at the intracranial segment oraround the hypoglossal canal, although a comparison

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with intraoperative stimulation findings has not yetbeen performed in man. However, in the cat it has beenshown that the site of magnetic excitation of thehypoglossal nerve is at the exit of the hypoglossalcanal (Kobayashi et al., 1999). In clinical practice, theproximal hypoglossal nerve can be excited with thecircular coil in a suboccipital position ipsilaterally tothe hypoglossal nerve. For stimulation of the left(right) peripheral nerve, side "B" ("A") of the circularcoil is viewed from the outside. However, magneticsuboccipital stimulation fails to evoke responses inabout 25% of subjects (Urban et aI., 1997c), which ismost probably due to the anatomical position of thehypoglossal nerve deep at the base of the skull. Highvoltage electrical stimulation using surface electrodesover the occipital skull may serve to overcome thisproblem as suggested by the results of a recently pub-lished study showing that supramaximal stimulation ofthe proximal hypoglossal nerve using this techniquewas possible in all 10 subjects (Kobayashi et al.,1999). The distal hypoglossal nerve can easily be stim-ulated supramaximally medial and posterior to theangle of the jaw with a conventional surface electricalstimulator (Redmond and Di Benedetto, 1988).

6.2.3. InterpretationIn healthy subjects, stimulation of one hemisphereevokes bilateral responses at both halves of the tongue(Muellbacher et al. 1994; Urban et aI., 1994; Meyer etal., 1997). Muellbacher et al, (1998) reported signifi-cantly higher amplitudes and shorter latencies for thecontralateral projections, while others did not findsignificant differences for these parameters betweenthe ipsilateral and contralateral projections (Meyeret al., 1997; Urban et al., 1997c). Since supramaximalelectrical hypoglossal nerve stimulation also elicits aslight muscle response (25-30% of the ipsilateralresponse) at the contralateral half of the tongue dueto volume conduction (Meyer et aI., 1997; Chenet al., 1999), the presence of some cross-talk has to beconsidered on cortical stimulation.

A supranuclear lesion of the corticolingual path-ways may be assumed, when: (1) no responses areobtained on motor cortex stimulation (no repro-ducible response for four consecutive trials with a

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gain of 200 (V/div); (2) the amplitude relationbetween motor cortex response and M-wave ampli-tude with electrical stimulation is 10%; and (3) adelayed CMCT or interside difference of the CMCT(> 2.5 SD from the normal mean) is observed.

7. Neuroanatomic studies

7.1. The course of corticofacial projections in thehuman brainstem

The course of corticofacial projections in the humanbrainstem was reconstructed in 53 patients with

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distal n. VII R

unifocal brainstem infarctions (Urban et al., 2oolb).At the midbrain and the pontomesencephalic level,infarctions with a lesion of the corticofacial projec-tions were located at the centre of the cerebralpeduncle. while the lesions at the upper and middlepontine levels extended across the centre of thepontine base (Fig. 1). The lesion sites at the lowerthird of the pons were found at a more ventromediallocation close to the midline. The distribution of thelesions within the pons indicates that the corticofacialfibres are split into a number of small dispersedfascicles. or show significant variability as to theirlocation within the base of the pons. Since the clinical

Buccinator L

distal n. VII L

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Fig. 1. MRI of a patient with contralateral central facial paresis due to a lesion of the left base of the pons. TMS of themotor cortex and stimulation of the proximal and distal facial nerve with recordings from the buccinator muscles (day 11after onset of symptoms). Stimulation of the left facial motor cortex (ipsilateral to the pontine lesion) evoked no response

in the contralateral buccinator muscle (from Urban et a1., 2001b).

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picture of patients with a lesion at the lower third ofthe pons was characterized by contralateral centralfacial palsy, it may be assumed that the corticofacialfibres cross the midline below this level. In threepatients with contralateral facial palsy, the lesionswere located in the middle and upper pons in aparalemniscal position at the dorsal edge of the pon-tine base (Fig. 2). This location correlates with histo-logical descriptions of an 'aberrant bundle', whichbranches off the main pyramidal tract at the midbrainand upper pontine level and reaches the facial nucleus

in a paralemniscal position (Hoche, 1898; Barnes,1901; Yamashita and Yamamoto, 2001).

Central facial paresis was also observed in fivepatients with upper medullary infarctions. Two ofthese patients showed left ventral medullary infarc-tion (Fig. 3) and contralateral central facial paresis,while the remaining three patients with lateralmedullary infarctions had central facial paresisipsilateral to the lesion with a supranuclear lesionpattern on TMS (Fig. 4). The distribution of thesemedullary lesions suggests that in some individuals

BuccInator R BuccInator L

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Fig. 2. MRI of a patient with isolated contralateral central facial paresis due to a lesion of the right dorsal base of thepons near the medial lemniscus. TMS of the motor cortex and stimulation of the proximal and distal facial nerve withrecordings from the buccinator muscles (day 12). Stimulation of the right facial motor cortex (ipsilateral to the pontine

lesion) evoked no response in the contralateral buccinator muscle (from Urban et al., 200lb).

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Buccinator R

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-....Fig. 3. MRI of a patient with left-sided ventral medullary infarction. TMS of the motor cortex and stimulation of the proximaland distal facial nerve with recordings from the buccinator muscles (day 10). Stimulation of the left facial motor cortex

(ipsilateral to the medullary lesion) evoked no response in the contralateral buccinator muscle (from Urban et al., 2001b).

the corticofacial fibres leave the lower pons and loopinto the ipsilateral ventral medullary region, cross themidline and ascend to the contralateral lateralmedullary region to reach the facial nucleus frombelow. A lesion of the corticofacial fibres located inthe lateral medulla oblongata beyond the midline thusexplains the occurrence of central facial palsy ipsi-lateral to the lesion side.

Two additional patients with dorsolateral medullaryinfarction also presented with facial paresis of

the central type. However, an electrophysiologicalexamination carried out 2 weeks later, revealedan incomplete facial nerve lesion with axonal degen-eration (Fig. 5). Thus, paresis of the central type maybe explained either by a lesion of the neurons of theorofacial muscles in the caudal part of the musculo-topically organized facial nucleus, or by a selectivelesion of infranuclear facial nerve fibres occurringalong the course of these nerves within the brainstem(Urban et al., 1999a).

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prox. n.VI R

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Fig. 4. MRI of a patient with left-sided lateral medullary infarction. TMS of the facial motor cortex and stimulation ofthe proximal and distal facial nerve from the buccinator muscle (day 10). Stimulation of the right motor cortex evoked no

response in the left buccinator muscle (from Urban et al., 2001b).

7.2. The course of corticolingual projections in thehuman brainstem

The course of corticolingual projections in the humanbrainstem was reconstructed in 30 patients withunifocal infarctions (Urban et al., 1996, 200lb,2002b). Similar to the corticofacial projections,infarctions with a lesion of the corticolingual projec-tions were located at the midbrain level at the centreof the cerebral peduncle, while the lesions at theupper and middle pontine levels extended across thecentre of the pontine base (Fig. 6). The lesion sitesat the lower third of the pons were located in a moreventromedial position close to the midline. In viewof the fact that patients with a lesion at the lowerthird of the pons also showed a lesion of the corti-

colingual projections, the lesion may be assumed tocross the midline below this level. No patient in thisgroup was found to have a lesion localized along thecourse of the 'aberrant bundle'.

In three patients with dorsolateral medullary infarc-tion, only the corticolingual fibres to the ipsilateraltongue were affected. This finding suggests that thecorticolingual projections were affected after leavingthe main pyramidal tract and crossing the midline ontheir way to the ipsilateral hypoglossal nucleus.

8. Dysarthria

The corticolingual projections are frequentlyimpaired in ischaemic dysarthria (Urban et al., 1997b,1999b, 200la). In a prospective study including 106

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Fig. 5. MRI of a patient with right-sided dorsolateral pontomedullary infarction. TMS of the motor cortex and stimula-tion of the proximal and distal facial nerve with recordings from the buccinator muscles (days 2 and 13). On day 2,stimulation of the left motor cortex evoked a prolonged and amplitude-reduced response in the contralateral buccinatormuscle, while the peripheral responses were within the normal range, suggesting a supranuclear lesion. On day 13, however,the CMAP amplitudes following right peripheral nerve stimulation were also diminished, demonstrating that the amplitude

reduction on cortical stimulation is due to a peripheral nerve lesion (from Urban et al., 2001b).

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.............Fig. 6. MRI of a patient with left-sided infarction of the pontine base with central facial palsy and dysarthria. TMS of

the left motor cortex (ipsilateral to the pontine lesion) evoked no response in both halves of the tongue.

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(a) Buccinator R Buccinator l (a) Buccinator R Buccinator L

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....Fig. 7. (a) Multiple sclerosis: Severe bilateraldelay of thebuccinator response latencies following stimulationof bothmotor cortices. Normal latencies following stimulation ofboth the proximal and distal part of the peripheral facialnerve. (b) Multiple sclerosis: Severe bilateral delay of thetongue muscle response latencies following stimulation ofboth motor cortices.Normal latencies followingstimulationof both the proximal and distal part of the peripheral

hypoglossal nerve.

Fig. 8. (a) ALS: Bilaterally absent buccinator muscleresponses on cortical stimulation while the CMAPs onperipheralfacial nerve stimulationare unaffected. (b) ALS:Bilaterally absent tongue muscle responses on corticalstimulation while the CMAPs on peripheral hypoglossal

nerve stimulationare unaffected.

9. Cerebral Ischemia

patients with sudden dysarthria due to a single occur-rence of ischemia, we showed that the corticolingualprojections at extracerebellar locations were affectedin 91% of patients, while other potentially speech-relevant projections were spared. However,comparable to ALS (Urban et al., 1998a) and corti-cobasal degeneration (Thiimler et al., 2003),dysarthria of other etiologies may also be associatedwith abnormal MEPs to the tongue. Thus, indysarthria without evidence of signs at other loca-tions, TMS of the tongue may contribute to thedetection of lesions and the identification of theunderlying pathophysiology of dysarthria.

The typical MEP pattern after cerebral ischemia ischaracterized by a reduced amplitude-quotient(MEP/M-wave-ratio) or an absent response duringmotor cortex stimulation, a raised motor threshold,and a slightly prolonged CCT (Weber and Eisen,2002). TMS findings in brainstem ischemia haverarely been reported. MEPs to the upper limbs onlywere examined in the largest reported series of 30patients in an intensive care unit, including patientswith brainstem infarction (n =15), space occupyingcerebellar infarction (n =5), brainstem or cerebellarhemorrhage (n =6), brainstem concussion (n =2),encephalitis (n = 1), and basilar aneurysm (n = I)

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352

responses in the acute stage (n =4), while almostfull motor recovery was observed in patients (n =2)where MEPs were obtained from the severelyparetic limbs. Ferbert et al. (1992) examined theMEPs to the small hand muscles in 20 patientswith hemiparesis due to pontine infarction. TMSwas performed in seven patients in the acutestage and in 13 patients in the chronic stage. Theauthors found a prolonged CMCT in patients with amoderate to severe degree of paresis, while the MEP/M-wave-ratio allowed no differentiation between theparetic and non-paretic side. From these observationsit may be concluded that MEPs performed in theacute stage of a brainstem stroke are of a prognosticvalue regarding the persisting functional motordeficit, comparable to that previously reportedfor MEPs of other brain regions (Heald et al.,1993; Arac et al., 1994; Turton et al., 1996; Cicinelliet al., 1997; Escudero et al., 1998; Trompetto et al.,2(00).

TMS studies may also contribute to localizinglesions within the nervous system. Although TMSenables the identification of the lesion location inthe axial plane, it allows only limited conclusionsconcerning the level at which the lesion is located inthe rostro-caudal direction. This is due to the fact thatthe MEPs fail to show whether the lesion is locatedwithin the brainstem or in the supratentorial region.However, if recordings are performed not only fromthe limbs, but also from cranial nerve innervatedmuscles (e.g. facial muscles, tongue), the lesionpattern allows some conclusions as to the lesion level,e.g. that the lesion should be located rostral from theuppermost pathological altered segment.

_R

.......-.-

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......... VlL

pl'Oll. n. VII L

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'proL n. VII R

_L

Day 14

Day 1

pl'Oll.n. VlIR

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Buccinator R

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(a)

(b)

Fig. 9. (a) Bell's palsy of the left side: On day 1, absentCMAP on magnetic stimulation of the proximal facialnerve and amplitude reduction in the buccinator muscleresponse on stimulation of the right facial motor cortex.(b) Bell's palsy of the left side: On day 14, absent CMAPon magnetic stimulation of the proximal facial nerve andincreasing amplitude of the buccinator muscle response onstimulation of the right facial motor cortex. Electricalstimulation of the left distal facial nerve shows amplitudereduction in the CMAP to 30% compared to the unaffected

side.

10. Multiple sclerosis

(Schwarz et al., 2(00). It has further been shownthat an absent response during motor cortex stimula-tion in the acute stage correlated significantly witha persisting motor deficit 3 months later. Bassettiet al. (1994) reported TMS findings to the upper andlower limbs of sixpatients with a locked-in syndromedue to bilateral brainstem infarctions. The motordeficit did not improve in the patients with absent

Characteristic TMS findings in patients with multiplesclerosis are prolongation of CMCT. reducedMEPIM-wave ratio, increased variability of onsetlatency of the MEP (latency jitter), and dispersedmorphology of the MEPs on motor cortex stimula-tion (Weber and Eisen, 2002). Involvement of thecorticobulbar projections have also been investigated

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353

Bucctn_R 8ucctnallllrL Ilucc:lnalDrR8__l

COIW. L _R_L co... R

prox.n.VII l

u>. ~r <:>: j,..

prox. It. VIIR

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Fig. 10. Multiple sclerosis: MRI showing demyelination in the left dorsolateral pons with peripheral facial palsy on theleft side. TMS on day 2 shows no response on cortical stimulation of the right motor cortex and normal peripheral nerveCMAPs, enabling the exclusion of Bell's palsy. Corresponding to the clinical recovery. TMS on day 14 shows a normal

motor response following right motor cortex stimulation and no axonal degeneration on peripheral nerve stimulation.

in multiple sclerosis, and demonstrated clinicallysilent lesions (Fig. 7a, b). However, in 30 patientswith known multiple sclerosis, MEPs of the cranialnerve muscles were associated with a lower proba-bility (40010) to disclose clinically silent lesionscompared to the upper (67010) and lower (80%)limbs, corresponding to the shorter length of thecentral projections which may be affected by ademyelinating lesion (Riepe and Ludolph, 1993;Urban et aI., 1994).

11. Amyotrophic lateral sclerosis (ALS)

TMS studies to the limbs frequently show a modestprolongation of CMCT, marked MEPIM-wave ratioattenuation and, in some cases, absence of MEPs. Ithas recently been shown by TMS that corticobulbar

tract function to the orofacial muscles (Urban et al.,1998), tongue (Urban et aI., 1998a), masseter(Trompetto et al., 1998; Desiato et aI., 2002) andtrapezius muscle (Truffert et aI., 2000) is frequentlyimpaired in the course of ALS (Fig. 8). Because thecorticobulbar and corticospinal tracts may beindependently involved in ALS (Bonduelle, 1975),the examination of both tracts in the diagnostic work-up is of special value to reveal upper motor neuroninvolvement (Urban et al., 2oo1c), and to differentiateALS from cervical spondylotic myelopathy (Truffertet aI., 2000). In a series of 51 consecutive patientswith different clinical patterns of ALS, a lesion ofthe corticolingual projections was observed in 53%,of the corticofacial projections in 47%, and of thecorticospinal projections to the upper and lower limbsin 25% and 43% of patients, respectively (Urban etaI.,2001c).

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354

12. Facial nerve palsy Day 2

Buccil\lltorR BuccinatorL

facial palsies, TMS is less suitable for the electro-physiological assessment of hypoglossal nervepalsies, because magnetic stimulation activates bothhypoglossal nerves across the cerebrospinal fluid, andeven in the presence of complete unilateral palsy asmall volume conducted muscle response from theintact half of the tongue is recorded. However, distal

] om'prox. n. VII L

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distal n. VII L

prox. n. VII L

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6 month

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Fig. 11. (a) Borreliosis with facial palsy on the right side.On day 2, bilaterally absent CMAPs on magnetic stimula-tion of the proximal facial nerve and amplitude reductionof the buccinator muscle response on stimulation of the leftfacial motor cortex. (b) Borreliosis with facial palsy on theright side. After six months, TMS continues to show bilat-erally absent CMAPs on magnetic stimulation of theproximal facial nerve, while the amplitude of the bucci-nator muscle response on stimulation of the leftfacial motor cortex is within the normal range. Electricalstimulation of the right distal facial nerve shows amplitudereduction in CMAP to 50% compared to the unaffected

side.

Fractionated examination of the corticofacial path-ways represents an essential contribution to thediagnostic work-up of facial palsies. Even in incom-plete Bell's palsy, canalicular stimulation of theproximal portion of the facial nerve frequently showsan absent or an amplitude reduced compound muscleaction potential (CMAP) within hours after theclinical onset of facial paresis due to a raisedstimulation threshold (Rosler et al., 1995) (Fig. 9).Local hypoexcitability is also observed in facialpalsies due to zoster oticus and borreliosis and istherefore, not specific to Bell's palsy. However, inother etiologies of facial palsy different MEP patternscan be observed in an early stage of the disease. Ininfranuclear facial nerve lesions due to a brainstemlesion, responses after cortical stimulation areaffected, although CMAPs following magneticstimulation at the proximal portion of the facial nerveare preserved (Urban et aI., 1998b) (Fig. 10).In borreliosis or malignant meningeosis, thecontralateral facial nerve may also show a subclinicalamplitude reduction in the CMAP with magneticstimulation (Rosler et aI., 1995) (Fig. II). In Guillain-Barre syndrome and hereditary motor and sensoryneuropathy type I (Charcot-Marie-Tooth type I) andtype ill (Dejerine-Sottas), prolonged latencies areobserved after cortical stimulation and proximalstimulation of the facial nerve (Rosler et aI., 1995,Glocker et al., 1999). Thus, the pattern of MEPabnormalities enables conclusions as to both thelesion site and the etiology. Since the local hypo-excitability on canalicular stimulation may persist formonths, even after complete clinical recovery fromfacial palsy, canalicular stimulation has no prognosticvalue (Glocker et al., 1994), in contrast to supra-maximal electrical stimulation 2 weeks after the onsetof facial palsy (Esslen 1977).

Peripheral hypoglossal nerve palsies occur lessfrequently compared to facial palsies. In contrast to

13. Hypoglossal nerve palsy

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stimulation of the affected hypoglossal nerve leadsto an amplitude reduction in the ipsilateral half,reflecting the extent of the axonal degeneration (Chenet aI., 1999).

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