The excitation site of the trigeminal nerve to transcranial magnetic stimulation varies and lies proximal or distal to the foramen ovale: An intraoperative electrophysiological study in man

Neurosciem'~' l, ettcrs, 141 (1992) 265 268

265

:c 1992 Elsevicr Scientific Publishers Ireland Ltd. All rights reserved 0304-3940/92/S 05.00

NSL 08777

The excitation site of the trigeminal nerve to transcranial magnetic stimulation varies and lies proximal or distal to the foramen ovale: an intraoperative electrophysiological study in man Urs D. Schmid, A a g e R. M o l l e r and J u d i t h S c h m i d Department o1' Neurological Surger3", Univer.~it3' qf Pitlshurgh School ~I' Medicilw, Pitt,~'hl4rgh. E4 15213 ( USA ) (Received 20 March 1992: Revised version received 3 April 1992: Accepted 24 April 1992)

Key words.

Trigcminal nerve: Neurography: Transcranial magnetic stimulation: Electrical stimulation

The excitation site of the trigeminal nerve using transcranial magnetic stimulation (magStim) was analyzed in 5 patients in whom the trigeminal nerve was surgically exposed in the posterior fossa during microvascular decompression of the facial nerve for hemifacial spasm. The trigeminal nerve was stimulated ( 1) magnetically immediately prior to craniotomy, and (2) electrically near the root exit zone (elREZ) of the nerve from the brainstem. Mean latency differences (A) of masseter c o m p o u n d muscle action potentials (CMAPs) (AelREZ minus magStiml were 0.7 (range: +0.3 to +1.3) ms (P<0.05, Wilcoxon-test). From these results, an analysis of anatomical data, and using a trigeminal nerve conduction velocity (NCV) of 50 m/s as reported in the literature, the following conclusions were drawn: the excitation site to magStim (1) is variable a m o n g individuals, (2) is located 3.4 (1.6 6.5) cm distal to the trigeminal REZ, and (3) which corresponds to segments ot" the nerve that are located either within or outside the cerebrospinal fluid (CSF), either proximal or distal to the foramen ovale. These findings are in contrast to those we obtained in a previous study of the facial nerve in which the excitation site was found to be constant a m o n g subjects and restricted to the location on the nerve where it exits the high conductivity CSF to enter the high-resistance petrous bone.

A rapidly varying magnetic field generated by brief current in a circular coil [1] applied over the parietooccipital surface of the scalp induces an electrical field that excites the ipsilateral trigeminal nerve within the cranium [2, 8, 12]. The site of excitation is unknown and has not been studied systematically, a shortcoming that prevents the technique from being useful in clinical and research settings. The aim of the present study was to localize the site of magneto-electrical excitation of the trigeminal nerve intraoperatively in patients in whom an unaffected trigeminal nerve could be stimulated electrically at its root exit zone (REZ) and magnetically under comparable physiological conditions. Five patients (2 men, 3 women: age 36 73, mean 46 years: 1 left, 4 right sides) who were undergoing posterior fossa operations for microvascular decompression (MVD) of the facial nerve to treat hemifacial spasm [6] participated in this study. Patients had no trigeminal neuropathy before or after surgery and were at low risk for complications from anesthesia. Stimulations and reCorre.spondem'e." U.D. Schmid, Department of Neurosurgery, Ludwig Maximilian University, Klinikum Grosshadern, D-8000 Mfinchen 70, FRG. Fax: (49)(89) 7095-8871.

cordings were performed while the patients were anesthetized by an anesthesia technique that facilitated intraoperative motor nerve studies [10]. The methods used in this study were approved by the Institutional Review Board of the University of Pittsburgh, and written consent was obtained from each subject to participate in the study. The trigeminal nerve was stimulated non-invasively using a commercially available magnetic stimulator ( M A G S T I M 200: The MAGST1M Co. Ltd., Whitland Industrial Estate, Whitland, Dyfed, SA34 OHR, UK). The stimulus characteristics of this device have been described earlier [11]. A standard stimulating coil with a mean diameter of 9.0 cm was used, through which a brief pulsed magnetic field with a maximal strength of 2.0 T was delivered. The coil placement over the parieto-occipital scalp [2, 8, 12], and the current flow in the coil were chosen individually for each patient to excite the trigeminal nerve at lowest threshold [2]. The cisternal segment of the trigeminal nerve was stimulated with a hand-held monopolar stimulation electrode [ 10] (Grass Instruments Co., Quincy, MA) using rectangular pulses of 0.15 ms duration at supramaximal intensities of 0.5 1.0 V. CMAPs were recorded with a pair of l-cm-long needle

266 TABLE l LATENCIES A N D A M P L I T U D E S OF MASSETER CMAPs TO TRANSCRAN1AL M A G N ETIC STIM U LATION (magStim) AN D D1R ECT E L E C T R I C A L STIMULATION OF THE REZ (REZStim) OF THE T R I G E M I N A L NERVE, A N D CALCULATED EXCITATION SITE Ot: M A G N E T I C STIMULATION AS D E T E R M I N E D BY DIRECT ELECTRICAL NERVE STIMULATION IN MAN Patient no.

I

2 3 4 5 Mean S.D. P-value*

Amplitude (mV)

Latency (ms)

magStim

REZStim

0.7 1.5 1.1 1.0 0.3

3.5 3.2 3.l 2.9 1.0

0.9 0.4

2.7 1.0

A REZStim minus magStim

Distance (cm)** between REZ and site of magStim

magStim

REZStim

A REZStim minus magStim

2.8 1.7 2.0 1.9 0.7

2.4 2.4 2.9 2.4 2.2

3.5 2.8 3.5 2.8 3.0

1.3 0.3 0.6 0.5 0.8

6.5 1.6 2.9 2.4 3.8

1.8 0.7 -<0.05

2.5 0.2

3.1 0.4

0.7 0.4 -<0.05

3.4 1.9

*Paired differences of masseter C M A P amplitudes or latencies, respectively (Wilcoxon-test). **Anatomical distance between the REZ and the site where magStim excites the trigeminal nerve, estimated with an NCV of 50 m/s, and using the latency difference REZStim minus magStim.

electrodes (Type E2, Grass) that were placed transcutaneously into the ipsilateral masseter muscle [10], the interelectrode distance was approximately 1-2 cm. Differential amplifiers (System 12, Grass) with filters set at 3 Hz and 3 kHz were used, and CMAPs were recorded on magnetic tape (FM recorder, Type B, A.R. Vetter Co., Rebersburgh, PA) at a tape speed of 15 inches/s and printed out on a laser printer for offline analysis. For the intraoperative experiments, the trigeminat nerve was stimulated magnetically 20-30 min after induction of anesthesia. The patient was then placed in a lateral decubitus position, the head was fixed in a 3-pin head-holder. The cerebellopontine angle (CPA) was opened through a suboccipital retromastoid approach, the facial and trigeminal nerves were exposed under continuous neuromonitoring [10], and the trigeminal nerve was stimulated electrically near its root exit zone at the brainstem. Then, MVD of the facial nerve [6] was completed. Vital signs remained within the physiological range during the pre- and intraoperative recording periods in all patients, and the individual body temperatures measured at the two times differed by -0.1 to +0.4°C. The courses of anesthesia and MVD were uneventful in all instances, and no patient had a neurological deficit of the trigeminal nerve after the operation. The data were analyzed as follows. Masseter CMAPs were studied that were of maximal amplitude with each stimulation modality. Baseline-to-peak amplitudes and onset latencies of CMAPs were measured, and paired arithmetic differences (/,I) were calculated between CMAP latencies and amplitudes to magStim and elREZ

stimulation. The significance of differences was tested with the Wilcoxon test for two matched samples [13]~ Table I gives the results we obtained in each individual. Fig. 1 shows a typical example of masseter CMAPs obtained in one individual. Comparing CMAP amplitudes to magStim and elREZ stimulation, it was found that even with the maximal stimulator output of 2 T and choosing optimal stimulus parameters, it was not possible with magStim to excite all trigeminal nerve fibers that contributed to the masseter C M A R Masseter CMAP latencies to magStim were consistently shorter than to eIREZ stimulation, and the differences were statistically significant. The results of this study confirm our previous findings [12] and those of others [2, 8] that the proximal segments m. M A S S E T E R

0.5 m V

elREZ

/ /

0,5mV

L / [

I

2

I

4

r

6

t

8

~

i0

I

12

I

14

I

16

I

18

I

20 m s

Fig. 1: Masseter CMAPs recorded in response to stimulation of the trigeminal nerve by transcranial magnetic (magStim) and direct electrical REZ stimulation (elREZ) during surgery•

267 Posterior ti)ssa

Middle cranial tbssa

Skull base V1 V2

V3

Porus trigemin.

Cavum Meckeli

Sinus Foramen cavernos, ovale

Fig. 2: Schematic view of the trigeminal nerve: root exit zone (REZ), pars compacta (P('), pars triangularis {PT), trigeminal ganglion (Ggl), third branch (V3 I. A dur~ duplication l\~rms the porus trigeminalis, the cavum Meckeli, and the lateral wall of the sinus cavernosus. Ccrebrospinal lluid ICSF) surrounds the PC and PT, but has no contact with the foramen ovale.

o f the trigeminal nerve can be excited non-invasively using transcranial magStim. In cadavers, the length o f the trigeminal nerve between the R E Z and the end o f the foramen ovale (Fig. 2) is between 3.2 cm [4] and 3.5 cm [7]. A b o u t 2.1 cm from the REZ, i.e. the pars compacta, the pars triangularis and the proximal surface o f the ganglion are surrounded by C S F [7], that extends from the posterior fossa t h r o u g h the porus trigeminalis into the c a v u m Meckeli [7]. Distal to the ganglion, the nerve lies outside the subarachnoid space, first in the lateral wall of the cavernous sinus, then in the foramen ovale, and finally extracranially in the fossa infratemporalis [7]. Supposing a N C V o f 50 m/s [3] in an u n d a m a g e d nerve, it can be calculated that magStim excited the trigeminal nerve 3.4_+ 1.9 (1.6 6.5) cm distal to the point o f electrical stimulation near the REZ. C o m p a r i s o n o f these calculated distances with the above anatomical data led us to conchide that the excitation site to magStim (1) is variable a m o n g individuals, and (2) lies either within, or outside the CSF, within a range o f some millimeters proximal or distal to the foramen ovale (Fig. 2). These findings are in contrast to the reports o f others who predicted that magStim excites the trigeminal nerve intracisternally [8] or at the R E Z [2]. With the stimulus parameters used in this study and in others [2, 8, 12], it seemed impossible to restrict excitation to a constant and anatomically well-defined segment o f the nerve. These conclusions differ from those we arrived at earlier when studying the facial nerve [11]: in that study the excitation site was ( 1) constant a m o n g subjects and (2) restricted to the end o f the labyrinthine segment o f the facial nerve. Transcutaneous stimulation o f nervous structures that lie deep within the neurocranium depends largely on the strength and orientation o f the applied stimulus, the re-

moteness o f the stimulated nerve fibers, and the specific impedances o f the surrounding tissues [9]. Because we have used analogous magnetic stimulation techniques to excite the facial [11] and trigeminal nerves, which originate in close anatomical proximity to each other [7], the above discrepancy m a y be explained by the difference in electrical impedance o f tissues surrounding these nerves. Nerve excitation occurs especially at sites where the induced electrical field changes most rapidly over distance [9], thus at anatomical boundaries between media o f high and low specific impedance. In the facial nerve, the highest impedance ratio between two media surrounding this nerve C S F and petrous bone can be found just at the end o f the labyrinthine segment of the facial canal [11]. F o r anatomical reasons [7] (Fig. 2), no such area o f immediate contact between C S F and bone can be found a r o u n d the trigeminal nerve. Here, impedances o f tissues change in small steps only [5], and this leaves the area o f lowest excitation threshold o f the trigeminal nerve illdefined and, therefore, focal excitation o f the trigeminal nerve is difficult or impossible to achieve with magStim. In view o f a clinical application o f this technique, it is concluded that: (1) it seems impossible to study reliably peripheral m o t o r conduction in the most proximal segments o f the trigeminal nerve. We cannot expect that slowed trigeminal nerve conduction resulting from focal pathology in the CPA, Meckel's cave, and/or the cavernous sinus would be detected reliably with trigeminal neur o g r a p h y by transcranial magStim" (2) similarly, estimation o f central m o t o r conduction ( C M C ) o f trigeminal pathways using transcranial magStim o f cortical and peripheral trigeminal m o t o r pathways has to be viewed with extreme caution: on the basis o f our data, trigeminal C M C would include conduction in a variable segment o f 3.2+ 1.9 cm of peripheral nerve, corresponding to peripheral conduction of 0.7_+0.4 ms (AelREZ minus magStim) in the present study. We thank Peter J. Jannetta, MD, and Hae D o n g Jho, M D , for permission to study patients under their care. The study was supported by the Swiss National Science F o u n d a t i o n (Grant no. 3.884.1.86), the Swiss Society for Medical-Biological Grants (Grant no. 703), the Swiss MS-Society (to U.D.S.): and the National Institute of Health (Grant no. 2-R01-NS21378) (to A.R.M.).

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