Transcranial Magnetic Stimulation: Estimation of the Motor System State in Patients with Brain Stem and Parastem Tumors

Gimranov R.F., Kurdyukova E.N.

Burdenko Research Neurosurgical Institute, Russian Academy of Medical Science, Russia

Introduction

Noninvasive and painless transcranial magnetic stimulation (TMS) [5] allows to carry out a more profound study of structural and functional peculiarities of the motor system (motor cortex and pyramidal pathways) [6, 8, 9]. Patients with brain tumors have organic and functional disorders in various functional systems, including the motor system [1, 4]. Determining motor thresholds (MT) and recording motor evoked potentials (MEVP) in TMS, one can assess a state of cortical motor neurons and pyramidal pathways [2, 10, 12].

The research was aimed at studying possible use of TMS under conditions of organic and functional disorders, watched in the motor system of patients with stem and parastem neoplasms before and after an operation. The obtained results were compared with those of healthy individuals.

Material and Methods

The study was carried out in 170 sick and 27 healthy individuals. All patients were divided into groups according to the following nosologic entities: a mass in the brain stem area - 104 cases, tumors of the cerebellopontine angle - 66 cases. The age of healthy individuals varied from 18 up to 37 years (27.5±8.3). All participants were informed about the study course and gave their written consent. TMS was accompanied by MT determination and MEVP recording.

Patients with a mass in the brain stem area were 4-57 years old (23.3±12.7). The mass was localized above the pons, at the level of the pons and below it in 37, 38 and 29 cases respectively. Symptoms were more marked on the right in 41 patients and on the left in 35 cases. MRI and CT findings were indicative of more frequent asymmetric localization of tumor as well. The age of patients with neoplasms of the cerebellopontine angle varied from 19 up to 61 years (35.3±16.3). According to MRI and CT examinations, tumors were localized on the right and left in 37 and 29 of them respectively. An operation for neoplasm removal was performed in all cases.

TMS of the right and left hemisphere, applied before and after operation (in 2-4 weeks), was accompanied by determining MT and recording MEVP from muscles of the right and left hands in all patients. The Cadwell MES-100 magnetic stimulator (USA), capable of inducing a pulse magnetic field of up to 2 T, was used (Fig.1). Pulse duration in TMS was equal to 0.1 ms. MEVP were recorded from m. abductor pollicis brevis. During stimulation we selected such a position of the stimulator coil, in which MEVP had maximum amplitude, minimum latency, constant form and configuration.

As for MT estimation, at first the coil optimum position and an angle of its placing ("a hot point"), characterized by maximum amplitudes and minimum latent periods of MEVP, recorded from the side opposite to TMS, were determined for relaxed muscles. It was followed by determination of motor thresholds in TMS with the help of increasing or reducing an induced magnetic field and intensity by 5%. MT was regarded as minimum intensity of TMS, in which there appeared marked responses, standing separately from a background muscular activity (the amplitude of not less than 0.5 mV and not more than 1 mV) in 3-5 consecutive presentations. MT values, determined in patients of different groups and healthy individuals were expressed as percent from maximum induction of the stimulator's magnetic field.

MP determination was followed by increase of induction of a magnetic field by 10-15% for stimulation of the maximum number of nervous elements with the purpose of obtaining responses with the highest possible amplitude. Estimation of MEVP amplitude and latency, recorded in magnetic stimulation of the cortex and spinal radicles, was carried out in the analogy with the method of stimulation myography (latency - a period of time between an impulse and response, amplitude - a response value between two peaks of MEVP).

Central time of motor conduction (CTMC) is total time, being a sum of time, during which an impulse spreads along corticospinal motor fibers (the pyramidal tract), and time, during which it is conducted along a proximal part of motor spinal radicles to a place of their appearance in intervertebral foramens at cervical and lumbar levels. TMS of the cortex, followed by magnetic stimulation of spinal radicles at the level of C5-C7, innervating hand muscles. CTMC was calculated as difference between latencies of common conduction time and peripheral conduction time (Fig.2).

Recording and analysis of MEVP in magnetic stimulation were carried out with the help of the Viking-IVP (Nicolet) eight-channel averaging device (Fig.3). Frequency band of an amplifier was equal to 30-3000 Hz; there were 4 series of averaging; an epoch of 150 msec was analyzed. Electrode impedance was less than 5 kOhm.

Non-parametric and parametric statistical analysis was carried out, using Statistica program (Student's t-criterion, Fisher's F-criterion). When p was less than 0.005, it was considered to be a significant index.

Results

Changes in the motor system of patients with brain tumors were estimated by comparison of MT values, amplitude and time of MEVP, watched in TMS, with analogous indices in healthy individuals. Motor thresholds in the latter group were characterized by asymmetry of their values. Average statistical values of MT in TMS of the left hemisphere were lower than in stimulation of the right hemisphere. Al healthy individuals were right-handed; thus, this phenomenon was only a reflection of functional asymmetry of the human brain.

MEVP of all healthy individuals, subject to TMS of the right and left hemispheres, were recorded from the left and right hands respectively. Amplitude and time indices, recorded in this group, did not differ to a considerable extent. There was no statistically significant difference in average values of MEVP in TMS of the left and right hemisphere. As for average values of latency of MEVP and CTMC in TMS of the right and left hemisphere, there was no reliable difference either (table 1).

Table 1

Average Statistical Indices of Motor Thresholds, Amplitude, Latency and Central Time of Motor Conduction in TMS in Healthy Individuals (M±m)

Indices

Stimulation on the Right

Stimulation on the Left

   Motor threshold

62.4±3.9 % (from 2 T)

59.8±4.4 % (from 2 T)

   MEVP amplitude

2.7±1.3 mV

2.8±1.3 mV

   MEVP latency

21.2±1.5 ms

21.2±1.4 ms

   CTMC

7.7±0.4 ms

7.6±0.4 ms

Motor thresholds were determined in all patients with brain tumors. There was a statistically significant increase of MT on both sides in comparison with the same indices in healthy individuals. MT values in TMS of the left hemisphere were lower than analogous indices in TMS of the right hemisphere. This difference was statistically reliable as well (table 2).

Table 2

Average Statistical Indices of Motor Threshold (% from 2 T) in TMS in Patients with Brain Tumors (M±m)

Patients with Tumors

Stimulation on the Right

Stimulation on the Left

   Brain stem

80.5±8.1 %

75.0±7.4 %

   Cerebellopontine angle

77.8±7.3 %

71.3±6.6 %

We managed to record MEVP from muscles of the left and right hands in TMS of the right and left hemisphere in all patients with brain stem tumors before operation. Comparison of average values of MEVP amplitude in these patients and healthy individuals revealed its reduction in the former group. However, this difference was statistically insignificant. Average values of latency of MEVP and CTMC were greater as compared with analogous indices in healthy persons. This difference was statistically reliable.

Comparison of average values of MEVP amplitude in patients with brain stem neoplasms before and after operation failed to reveal any statistically significant difference, though it tended to some increase. Reduction of MEVP latency after operation was statistically reliable. At the same time there was reliable decrease of average values of CTMC along the pyramidal tract (table 3).

Table 3

Average Statistical Indices of MEVP Amplitude and Time in Patients with Brain Stem Tumors before and after Operation (M±m)

Indices

Stimulation on the Right

Stimulation on the Left

   MEVP amplitude before operation

1.4±0.8 mV

1.3±0.8 mV

   MEVP latency before operation

26.5±4.7 ms

27.1±5.1 ms

   CTMC before operation

9.8±2.1 ms

9.9±1.9 ms

   MEVP amplitude after operation

1.5±0.8 mV

1.6±0.9 mV

   MEVP latency after operation

22.8±2.5 ms

21.9±2.9 ms

   CTMC after operation

8.6±1.8 ms

8.4±2.2 ms

Symptoms were more marked on the right (41) or on the left (35) in 76 out of 104 patients with brain stem tumors. Usually MRI and CT examinations were indicative of asymmetric localization of tumor. The analysis of amplitude and time indices of MEVP in stimulation of patients with brain stem tumors and dominant right- and left-side symptoms revealed asymmetry of responses. Comparison of average values of MEVP amplitude in patients before operation and healthy individuals showed, that there was its reliable reduction on the side of neoplasm localization. No difference was watched on the opposite side. Before operation average indices of MEVP latency in patients with brain stem tumors, localized on the right and left, were reliably bigger on the side of a lesion than analogous parameters in healthy individuals. They became smaller on the affected side after operation. Reliable growth of average values of CTMC was watched on the side of tumor localization, as compared with analogous indices, typical of healthy individuals. The operation resulted in their reliable reduction. As for the intact side, there was no considerable difference in values of CTMC before and after operation (Table 4).

Table 4

Average Statistical Indices of MEVP Amplitude and Time in Patients with Right- and Left-Side Localization of Brain Stem Tumors before and after Operation (M±m)

Indices

Brain Stem Tumors (on the right)

Brain Stem Tumors (on the left)

¯

TMS
(on the right)

TMS
(on the left)

TMS
(on the right)

TMS
(on the left)

   MEVP amplitude before operation

1.7±0.7 mV

2.1±1.3 mV

2.2±1.1 mV

1.8±0.6 mV

   MEVP latency before operation

27.6±3.8 ms

25.4±2.9 ms

25.7±2.7 ms

28.1±3.9 ms

   CTMC before operation

10.3±2.2 ms

8.9±1.3 ms

9.1±2.1 ms

10.1±2.1 ms

   MEVP amplitude after operation

1.9±1.0 mV

2.2±1.1 mV

2.3±1.2 mV

2.0±0.9 mV

   MEVP latency after operation

23.1±3.2 ms

22.3±2.9 ms

22.1±2.7 ms

22.9±3.1 ms

   CTMC after operation

8.9±1.4 ms

7.9±0.9 ms

7.8±1.2 ms

8.7±1.3 ms

MEVP were recorded in all patients with neoplasms of the cerebellopontine angle. Comparison of average values of MEVP amplitude in patients and healthy individuals reveled no significant difference, though it tended to some reduction.

Average values of MEVP latency were bigger in patients, as compared with healthy individuals, but this difference was statistically insignificant. However, there was statistically reliable increase of average indices of CTMC in patients, when TMS of the right and left hemisphere was carried out. Comparison of average values of MEVP amplitude in patients with tumors of the cerebellopontine angle before and after operation revealed no significant difference. These patients had reliable decrease of average indices of MEVP latency. There was statistically significant reduction of CTMC after operation (table 5).

Table 5

Average Statistical Indices of MEVP Amplitude and Time in Patients with Tumors of the Cerebellopontine Angle before and after Operation (M±m)

Indices

TMS on the Right

TMS on the Left

   MEVP amplitude before operation

2.2±1.1 mV

2.1±1.1 mV

   MEVP latency before operation

23.2±3,3 ms

23.4±3.2 ms

   CTMC before operation

8.0±1.2 ms

7.9±1.2 ms

   MEVP amplitude after operation

2.1±0.9 mV

2.1±1.1 mV

   MEVP latency after operation

22.6±3.4 ms

22.3±2.9 ms

   CTMC after operation

7.5±1.2 ms

7.4±1.1 ms

Tumors of the cerebellopontine angle were characterized either by marked dislocation and compression of the stem in the posterior cranial fossa or its S-shaped distortion and torsion. Pons varolii and medulla oblongata were atrophic and thin; this phenomenon was especially typical of the tumor side (Fig.4). Sometimes changes in hemispheres were asymmetric too; they were more marked on the tumor side.

Separate analysis of amplitude and time indices of MEVP in patients with tumors of the cerebellopontine angle, located on the right and left, proved an effect of tumor localization on them. Comparison of average values of MEVP amplitude in these patients before and after operation and in healthy individuals demonstrated its reliable reduction on the side of tumor localization. At the same time there was no difference on the opposite side. Before operation average indices of MEVP latency in patients were reliably bigger on the side of lesion in comparison with analogous parameters in healthy individuals. After operation amplitude increase and latency reduction of MEVP were watched on the affected side (Fig.5). There was a reliable growth of average values of CTMC on the lesion side as compared with healthy persons. They reduced after operation. As for the intact side, we failed to reveal any considerable difference in values of CTMC before and after operation. (table 6).

Table 6

Average Statistical Indices of MEVP Amplitude and Time in Patients with Tumors of the Right and Left Cerebellopontine Angle before and after Operation (M±m)

Indices

Neurinoma of the Right VIII Nerve

Neurinoma of the Left VIII Nerve

¯

TMS
on the Right

TMS
on the Left

TMS
on the Right

TMS
on the Left

   MEVP amplitude before operation

1.5±0.5 mV

2.3±1.1 mV

2.4±1.2 mV

1.5±0.7 mV

   MEVP latency before operation

23.6±3.4 ms

22.2±2.2 ms

22.7±2.8 ms

24.1±3.7 ms

   CTMC before operation

8.3±0.9 ms

7.8±1.3 ms

7.9±1.2 ms

8.1±1.3 ms

   MEVP amplitude after operation

2.2±1.1 mV

2.2±1.0 mV

2.3±1.1 mV

2.2±0.9 mV

   MEVP latency after operation

22.6±2.6 ms

22.2±2.6 ms

22.0±2.5 ms

22.8±3.3 ms

   CTMC after operation

7.9±1.2 ms

7.6±0.9 ms

7.6±1.2 ms

7.7±0.9 ms

Discussion

One of the former studies, carried out in 30 right-handed and 30 left-handed persons aged 21-57, proved, that a motor threshold for the biceps and musculus flexor pollicis longus was lower in stimulation of a dominant hemisphere [16]. Our results confirm, that MT, causing MEVP in TMS of a dominant hemisphere of healthy individuals, is lower. Thus, they agree with data, given in literature [11]. This difference is likely to be of a functional character, as this asymmetry disappears with aging, when a smaller functional load is applied to a dominant hand [10]. Increase of MT values in patients with brain stem tumors can result both from primary dysfunction of corticospinal tracts and secondary dysfunction of the motor cortex.

It is known, that various pathologic processes, affecting the motor system, result in changes MT and MEVP in TMS of patients [3, 12, 13, 14, 17]. TMS, as a diagnostic modality, should be used in patients with brain tumors with great care to ensure its safety (gradual increase of induction of a magnetic field and longer intervals between stimulation sessions). Besides, one should take into account the existing "safety scale" [3].

Recording of MEVP in patients with tumors of the cerebellopontine angle and brain stem during TMS showed, that localization of neoplasm, its size and a degree of its pressure on efferent pathways of the brain stem had an impact on time and amplitude indices of responses. More marked changes of time and amplitude parameters of MEVP during stimulation were watched in patients with brain stem tumors. Maybe, it can be explained by the fact, that there was more time for activation of compensatory processes in parastem neoplasms. There were reliable increase of average statistical indices of CTMC and reduction of amplitude of MEVP in both above-mentioned groups of patients, as compared with analogous data, obtained in healthy individuals. Changes of amplitude and time of MEVP in various diseases of the CNS are the most widespread electrophysiologic phenomenon [15, 18]. It is in line with the results of our investigation.

The operation and removal of tumor resulted in smaller compression of the brain stem. It manifested itself in changes of amplitude and time values of MEVP (amplitude increase and decrease of latency time). Reduction of latency time and CTMC after the operation reflects improvement of conduction along the pyramidal tract.

Changes of time parameters of MEVP in TMS can be regarded as primary. As for changes of MT and MEVP amplitude in patients with stem and parastem neoplasms, they are almost sure to be secondary. A high degree of plasticity of the motor cortex in various disorders of nervous impulse conduction has already been reported [3, 7, 8]. Thus, improved conduction of nervous impulses (afferent and efferent) along conduction tracts in the brain stem and increase of MEVP amplitude in TMS are likely to be the result of plastic reorganization, which takes place in the motor system.

Further research with TMS application, aimed at studying organization of the motor system, will allow to specify mechanisms, which lead to its dysfunction, as well as mechanisms, which cause its functional restoration after removal of brain tumors of different localization.

REFERENCES

  1. Gimranov R.F. Magnetic stimulation in diagnosis of lesions of the nervous system. In: Neurophysiologic Research under Conditions of a Clinic. Edit. by Shchekutyev G.A. - Moscow: Antidor., 2001. - P. 163-179 (Rus.).
  2. Gimranov R.F. Study of thresholds of motor responses in transcranial magnetic stimulation in healthy individuals and patients with brain tumors // Zhurnal Phisiologii cheloveka. - 2002. - V. 28, N 4. - P. 38-41 (Rus.).
  3. Gimranov R.F. Transcranial magnetic stimulation. Moscow: Allana, 2002. - 164 p. (Rus.).
  4. Samoilov V.I. Diagnosis of brain tumors. Moscow: Medicine, 1985. - 304 p. (Rus.).
  5. Barker A.T., Jalinous R. And Freeston I.L. Non-invasive magnetic stimulation of human motor cortex. // Lancet. - 1985.- V.1. - P.1106-1107.
  6. Di Lazzaro V., Oliviero A., Berardelli A., Mazzone P., Insola A., Pilato F. Direct demonstration of the effects of repetitive transcranial magnetic stimulation on the excitability of the human motor cortex // Exp.Brain Res.- 2002. - V.144. - P. 549-553.
  7. Fraser C., Power M., Hamdy S., Rothwell J., Hobday D., Hollander I., Tyrell P., Hobson A., Williams S., Thompson D. Driving plasticity in human adult motor cortex is associated with improved motor function after brain injury // Neuron. - 2002. - V. 34 - P. 831-840.
  8. Hess C.W., Mills K.R., Murray N.M.F. Measurement of central motor conduction in multiple sclerosis by magnetic brain stimulation // Lancet. - 1986. - V.2 - P. 335-358.
  9. Ingram D.A., Swash M. Central motor conduction is abnormal in motor neuron disease // J.Neurol.Psychiatr. - 1987. - V. 50 - P.159-166.
  10. Matsunga K., Uozumi T., Tsuji S., Murai Y. Age-dependent changes in physiological threshold asymmetries for the motor evoked potential and silent period following transcranial magnetic stimulation // EEG and clinical Neurophysiology. -1998. - V.109 .- P. 502-507.
  11. Macdonell R.A.L., Shapiro B.E., Chiappa K.N., Helmers S.L., Cros D., Day B.J., Shahani B.t. Hemispheric threshold differences for motor evoked potentials produced by magnetic coil stimulation. // Neurology. - 1991. - V. 41. - P. 1441-1444.
  12. Roricht S., Meyer B.U. Residual function in motor cortex contralateral to amputated hand // Neurology. - 2000. - V. 54. - P. 984-987.
  13. Reutens D.C., Berkovic S.F. Increased cortical excitability in generalized epilepsy demonstrated with transcranial magnetic stimulation // Lancet. - 1992. - V. 339. - P. 362-363.
  14. Reutens D.C., Puce A., Berkovic S.F. Cortical hyperexcitability in progressive myoclonus epilepsy: a study with transcranial magnetic stimulation // Neurology. - 1993. - V. 43. - P. 186-192.
  15. T2 Tang S.F., Ren Z.Y. Magnetic transcranial motor and somatosensory evoced potentials in cervical spondilitic myelopathy // Clin.Med .J. - 1991. - V. 104. - P. 409-415.
  16. Triggs W.J., Calvamo R., Macdonell R.A.L., Cros D., Chiapa K.H. Physiological motor asymmetry in human handedness evidence from transcranial magnetic stimulation // Brain Res. - 1994. - V. 636. - P. 270-276.
  17. Vitek J.L. Pathophysiology of dystonia: a neuronal model // Mov. Disord. - 2002 .- V. 3. - P. 49-62.
  18. Ying Z., Schmid U.D., Schmid J., Hess C.W. Motor and somatosensory evoked potentials in coma: Analysis and relation in clinical status and outcome // J.Neurol., Neurosurg. and Psychiat. - 1992. - V.55. - P. 470-474.