25
CliniculNeurologycmdNeurosurgery.94 (I 992) 25-30 0 1992Elsevier Science Publishers B.V. All rights reserved 0303-8467/92/$05.00
CLINEU
00179
The prognostic value of intra-operative observations during thalamotomy for parkinsonian tremor K. Wester” and E. Hauglie-Hanssenb Departments of Neurosurger.v, “Haukeland Sykehus, University of Bergen Medical School, Bergen, Norway, and bRikshospitalet, University of Oslo Medical School, Oslo, Norway (Received (Revised,
(Accepted
Key words:
Brain stimulation;
Parkinson’s
disease;
19 March,
1991)
received 29 July, 1991) 26 August,
Stereotaxic
1991)
techniques;
Thalamotomy;
Tremor
Summary Data from 27 thalamotomies observations and the long-term electrodes
in the target
threshold
intensities
were analyzed with respect to possible correlations between certain intra-operative effect on parkinsonian tremor. Tremor reduction caused by mechanical impact of the
area was not correlated
during
the intra-operative
with the long-term electrical
stimulation
effect on the tremor. of the target
The same was true for the
area,
stimulation
that
facilitates
and/or inhibits the tremor. In a minority of the patients, all with good long-term results, a combination of a pronounced tremor inhibition from the electrode insertion and a low threshold intensity was observed. Variations in other lesion parameters were not correlated with the outcome. The results are discussed within the framework of a “tremor” vs. a “tonus” mechanism underlying the thalamotomy effect.
Introduction
most effective target area in a possible tremorogenic tremor-mediating part of the diencephalon.
Stereotaxic thalamotomy is a well established symptomatic treatment for parkinsonian tremor and other
An acute oedema surrounding the lesion may attribute to the immediate inhibitory effect on tremor by tempo-
movement
rarily blocking
disorders.
The majority
of patients
resistant parkinsonian tremor benefit tion [l-13]. In a few cases, however,
with drug-
from this operathe tremor may
neural elements
gradually be reactivated, tremor. The postoperative
permanent tremor relief. The cause of the tremor
1). Provided
is not
known. However, it seems reasonable to suspect the lesion to have been too small and/or placed outside the
Correspondenceto: Dr. Knut Wester, Department Haukeland
Sykehus,
N-5021 Bergen. Norway.
of Neurosurgery,
in tremor
mech-
anisms. As the oedema subsides and natural repair processes take place, parts of the tremor mechanisms may
eventually reappear. This may happen also after excellent immediate results, in spite of apparently identical operative procedures as those performed in cases with relapse in these patients
involved
or
sive compared
causing reappearance oedema can be rather
with the volume
the concept
of the lesion proper
of a tremorogenic
thalamic
of the exten(Fig. area
is of some validity, one would expect this to be reflected in intra-operative observations. Although seldom discussed in scientific reports, most neurosurgeons performing thalamotomy probably assume this to be the case. As few have access to refined neurophysiological recording techniques [ 14-201, peroperative stimulation studies is the most common method for physiological
26
Fig. 1. Horizontal CT scans showing the maximal extent of the thalamic lesion 1 day (left) and 4 months (right) postoperatively. Note
the oedematous zone surrounding the inner core of the lesion.
target confirmation. Electrical stimulation of the target area may have dramatic effects on tremor (Fig. 2), and the threshold intensity for eliciting these effects can be determined (Fig. 3). Low threshold intensities are logically considered to indicate proximity to the optimal target area, and should therefore predict a successful lesion. When the electrodes are inserted into the target area, reduction or arrest of tremor is often observed (Fig. 4). This is presumably due to mechanical impact on neural elements, and is regarded as another promising sign, indicating a good long-term result. In the present study, we have analyzed whether these effects or other peroperative factors could be attributed to any prognostic significance for the final outcome of the operation.
larger sample of patients described elsewhere [I 31. Only those who had been operated on under standardized intra-operative conditions were selected. One patient was operated twice due to reappearance of the tremor; thus the total number of operations included was 27. Surgery
A detailed account for the surgical procedures is given elsewhere [13]. The thalamic target was located 2 mm behind the mid-commissural plane, 3 mm above the inter-commissural line and, most commonly, 14 mm laterally from the mid-sagittal plane. Two electrodes were used, 6 mm apart, the active tips measuring 2 mm. The inter-electrode plane was approximately parallel to the internal capsule. With the pre-selected target area, stimulation and lesioning was assumed to affect the ventrooral (v.o.a. and v.0.p.) and the reticular thalamic nuclei
VI. Material and methods
The lesions were calculated to be of the same size as those reported by Hirai et al. [6].
Patients
Twenty-six patients with parkinsonian tremor (age 49-73 years, median 64) were selected from a slightly
Recording
The tremor was recorded continuously
by means of
27
Fig. 2. Polygraph recordings showing effects of stimulation in the left thalamus on tremor in the contralateral (right) index finger. Stimulation parameters: 1.O mA, 50 Hz, 1.O msec. Upper trace: Time in set with stimulus marker (horizontal bar). Middle trace: left index finger (no tremor). Lower trace: right index finger. Left: arrest of ongoing tremor at the onset of stimulation. of tremor when stimulating with the same parameters against a background of no tremor.
mechano-electrical transducers mounted of both index fingers (see Figs. Z-4). Stimdution Prior to lesioning,
on the dorsum
the target area was screened
larily from a constant-current
stimulator
or (4) absent. In the final evaluation,
were grouped together as “good” results.
as “poor”
(1) and (2)
results, and (3) and (4)
for ef-
fects on tremor as well as for unwanted side effects by electrical stimulation. The stimulus was delivered bipopulses, pulse width
present,
Right: initiation
(50 Hz biphasic
1.O msec).
Results The present
paper deals only with the effect of the tha-
lamotomy on the tremor per se. According to the criteria given above, 5 of the operations were found to have
Ewluation of long-term t@cts All the patients were re-admitted
to our department
given “poor”, and 22 “good” results. This corresponds exactly with our own evaluation at the post-operative
for a 3-month post-operative control. However, to avoid possible bias on the authors’ part, the final evaluation was left to the patients’ referring neurological depart-
control
3 months
IZfjxt
qf’elrctrode
ment
(median 17) months (see ref. 13 for details). Among other questions, they were asked to indicate
In 14 operations, insertion of the electrodes into the target area caused a pronounced reduction of the tremor, i.e. an amplitude reduction of 50% or more. lasting for
whether the tremor, at the most recent visit, was (1) prc~mt (It ,fklI strength. (2) nlodwate!)~ presrnt, (3) slight!\,
minutes (Fig. 4). In a few cases, the tremor was almost abolished for the rest of the operation. In the remaining
after
_- ,--.%._ W-_-S_
a post-operative
observation
time
of 3-31
-....-q~.----I_
._-.--
after surgery. insertion
-.
------__a..----.
Fig. 3. Example of determination of threshold intensity. Same patient and stimulation parameters as in Fig. 2. Horizontal bars indicate thalamic stimulation with the following intensities (in mA, from left to right): 0.60. 0.55. 0.60. 0.80. 0.90. Note also the decreasing latencies with increasing stimulus intensities.
*_., -- ._ ._ A
-
-A
Fig. 4. Marked reduction of tremor in the left index finger (lower trace) induced by mechanical insertion (between arrows) of the electrodes from the cortical surface into the target in the right thalamus. Due to higher amplitude of the left-sided tremor, the gain in this trace is reduced 5-fold.
13 operations,
this effect was not convincingly observed, or it was less pronounced. In the analyses below, this mechanical effect was accordingly classified as being “pronounced” or “weak or absent”. The 2 result groups (“good” and “poor”) did not differ with respect to the presence or absence of mechanical insertion effect (Table 1).
and “poor”) did not differ significantly. either when tested on a ranking scale (Mann-Whitney U-test). or when tested with the Fischer exact probability test (Table 2). The combination of mechanical insertion ejfect and loo. threshold intensity In a minority of the operations, a pronounced mechanical insertion effect and a low threshold were both observed. All these operations had good long-term results (Table 3). This correlation approaches the level of statistical significance (x2 = 3.25, P = 0.07).
Stimulation effkcts Electrical stimulation of the ventrolateral thalamus most often had a dichotomic effect on the contralateral tremor. With the hands resting comfortably, stimulation most often elicited a typical parkinsonian tremor. When stimulating against a background of positional tremor, obtained by asking the patient to elevate his arms, identical stimulation could cause a prompt arrest of tremor (Fig. 2). The threshold intensities for eliciting these effects were found to vary between 0.5 and 2.0 mA, with a median of 1.25 mA. Threshold intensities below or above this median were classified as being “low” or “high”, respectively. Threshold intensities for the 2 result groups (“good”
Other factors The long-term results did not correlate with parameters relating to the size of the lesion (maximal heating time, temperature or total extent of the lesioned area).
TABLE I
TABLE 2
TREMOR-REDUCING EFFECT OF ELECTRODE INSERTION IN THE TARGET AREA VS. LONG-TERM EFFECT OF THE OPERATION -
THRESHOLD INTENSITIES FOR STIMULATION EFFECTS ON TREMOR VS. LONG-TERM EFFECT OF THE OPERATION
Insertion effect
Threshold intensity
Long-term effect of the operation Good
Poor
Pronounced Weak or none
12 9
2 4
Total
21
6
Discussion Although not commonly mentioned in the literature, it
Long-term effect of the operation Good
Poor
Low High
12 9
2 4
Total
21
6
29 TABLE 3
lesions for a wide variety of dyskinesias
COMBINED FACTORS (EFFECT OF ELECTRODE SERTION AND LOW THRESHOLD INTENSITIES) LONG-TERM EFFECT OF THE OPERATION
INVS.
understand
targets
ful targets
21
6
although thalamic
mal movements
subdivision
neurosurgeons
perform-
ing thalamotomies that substantial tremor reduction, when the electrode is inserted into the target, is a good omen, as it is when electrical stimulation of the target affects tremor
even at low intensities.
these assumptions tremorogenic or
The logic behind
must be that there exists a restricted tremor-mediating diencephalic area,
and that the effect of the operation lesion is to this area.
to
throughout has yet been
clinical
targets.
can alleviate character
in different
abnor-
and etiol-
parts of this digood effects
These facts are difficult
of a restricted
on Use-
to ex-
and specific tremor
mechanism. The present
among
widely
seem to have equally
tremor.
plain by the existence
opinion
operations.
no attempt lesions
of different
on parkinsonian
,$ = 3.25. P = 0.01.
is a wide-spread
scattered
ogy, and vice versa: lesions encephalic
of symptoms. Laitinen’s [22] survey
the results of using different
identical
to the
in a specific tremor mechanism
are apparently
the diencephalon, Thus,
in addition
[I 31. It is difficult
for tremor-alleviating
made to compare 0 6
and rigidity
how lesions
preferred
Poor
Low threshold und pronounced insertion 8 effect 13 Other operations Total
tremor
should alleviate such a variety More doubt emerges from
Long-term effect of the operation Good
parkinsonian
is better the closer the
The concept of a restricted tremorogenic area receives support from the electrophysiological works of AlbeFessard [14], Jasper [16], Ohye [18,19] and others [17,20]. In his microelectrode studies, Ohye has demonstrated thalamic (Vim) cells that fire in a synchronous fashion
results, especially
those from the stimula-
tion studies, are similarly difficult to explain within the concept of such a mechanism. To us, the presently available data seem to favour some sort of “tonus” rather than a “tremor” mechanism theory. Such a tonus mechanism may possibly play on the muscular tone [23]. There is also evidence that this part of the thalamus may play some part in the attentional tone [24-291. The proximity of the target
area
such as the reticular this context.
to non-specific nucleus,
thalamic
is of particular
structures, interest
in
The prognostic value of the intra-operative observations described here seems to be of limited importance. One can relatively safely predict a good long-term outcome if a pronounced insertion effect and a low threshold intensity appear in combination. However, excellent re-
with the tremor. These cells are located in the same thalamic subdivision, or even within the same nucleus where
sults may occur without
lesions can alleviate tremor. It is therefore possible that these cells “are involved in the tremor-mediating system.
Acknowledgements
if not in the tremor genesis” [18]. However, such observations cannot be taken as evidence for a causal relation-
The authors wish to thank professor E.-O. Backlund for his invaluable criticism and comments, and Dr. M.
ship between
Lund-Johansen
the two phenomena,
with the thalamic
unit
firing being the primary event. On the contrary, it may well be that the thalamic cell activity is merely reflecting the peripheral muscle activity associated with the tremor, thus being a secondary event. Ohye has himself demonstrated that such units can be driven by stretching muscles
involved
in the tremor
[18].
There are also intriguing facts that undermine the notion of a restricted tremorogenic area in the thalamus. Lesions in the same area can alleviate a number of different movement disorders. also when tremor is not involved [20]. We have ourselves used identical thalamic
this combination.
for technical
assistance.
References Tasker. R.R., Siqueira, J., Hawrylyshyn, P. and Organ, L.W. (1983) What happened to VIM thalamotomy for Parkinson’s disease? Appl. Neurophysiol.. 46: 68883. Broggi, G., Giorgi, C. and Servello, D. (1987) Stereotactic neurosurgery in the treatment of tremor. Acta Neurochir., Suppl. 39: 13-16. Van Buren, J.M., Li, C.-L.. Shapiro, D.Y.. Henderson, W.G. and Sadowsky, D.A. (1973) A qualitative and quanti-
4
5
6
7
8
9
10
11
12
13
14
15
16
tative evaluation of Parkinsonians three to six years following thalamotomy. Confin. Neurol., 35: 202-~235. Frank, F., Fabrizi, A.P., Frank-Ricci, R. and Gaist, G. (1987) Stereotaxis and abnormal movements. Acta Neurochir Suppl. 39: 66-69. Gillingham, F.J., Watson, W.S. and Donaldson, A.A. (1960) The surgical treatment of parkinsonism. Br. Med. J.. 2: 139551402. Hirai, T.. Miyazaki, M., Nakajima. H., Shibazaki, T. and Ohye, C. (1983) The correlation between tremor characteristics and the predicted volume of effective lesions in stereotaxic nucleus ventralis intermedius thaiamotomy. Brain, 106: 1001-1018. Hitchcock, E., Flint, G.A. and Gutowski, N.J. (1987) Thalamotomy for movement disorders: a critical appraisal. Acta Neurochir., Suppl. 39: 61- 65. Kelly, P.J.. Ahlskog, J.E., Goerss, S.J.. Daube, J.R., Duffy, J.R. and Kall, B.A. (1987) Computer-assisted stereotactic ventralis lateralis thalamotomy with microelectrode recording control in patients with Parkinson’s disease. Mayo Clin. Proc., 62: 6555664. Kelly, P.J. and Gillingham, F.J. (1980) The long-term results of stereotaxic surgery and L-dopa therapy in patients with Parkinson’s disease. A lo-year follow-up study. J. Neurosurg., 53: 332-337. Van Manen, J., Speelman, J.D. and Tans, R.J.J. (1984) Indications for surgical treatment of Parkinson’s disease after levodopa therapy. Clin. Neurol. Neurosurg., 86: 207-212. Matsumoto, K., Shichijo, F. and Fukami, T. ( 1984) Longterm follow-up review of cases of Parkinson’s disease after unilateral or bilateral thalamotomy. J. Neurosurg., 60: 1033-1044. Williams, A. and Caine, D.B. (1981) Treatment of parkinsonism. In: Barbeau, A. (Ed.), Disorders of Movement, MTP Press, Lancaster, pp. 171-190. Wester, K. and Hauglie-Hanssen, E. (1990) Stereotaxic thalamotomy - experiences from the levodopa era. J. Neurol. Neurosurg. Psychiat., 53: 427-430. Albe-Fessard, D.. Arfel, G. and Guiot. B. (1963) Activites electriques characteristiques de quelques structures cerebrales chez l’homme. Ann. Chir., 17: 1185-1214. Gaze, R.M., Gillingham, F.J., Kalyanaraman, S., Porter, R.W., Donaldson, A.A. and Donaldson, I.M.L. (1964) Microelectrode recordings from the human thalamus. Brain. 87: 691-706. Jasper, H.H. and Bertrand, G. (1966) Thalamic units involved in somatic sensation and voluntary and involuntary movements in man. In: Purpura, D.P. and Yahr, M.D.
I7
18
19
20
21 22
23
24
25
26
27
28
29
(Eds.), The Thalamus. Columbia I ‘III\. Press. Ncu York. NY, pp. 3655390. Narabayashi, H.. Maeda, T. and Yokochi. 1.. ( 1987) Longterm follow-up study of nucleus ventralis intermedius and ventrolateralis thalamotomy using a microelectrode technique in parkinsonism. Appl. Neurophysiol.. 50: 330. 337. Ohye, C. (1988) Selective thalamotomy for movement disorders: microrecording stimulation techniques and results. In: Lunsford, L.D. (Ed.). Modern Stereotactic Neurosurgery, Nijhoff, Boston, MA. pp. 3 15 -33 I. Ohye, C. and Albe-Fessard. D. (1978) Rythmic discharges related to tremor in humans and monkeys. In: Chalazonitis, N. and Boisson, M. (Eds.). Abnormal Neuronal Discharges, Raven Press, New York, NY, pp. 37 4X. Tasker, R.R., Yamashiro, K., Lenz. 1:. and Dostrovsky, J.O. ( 1988) Thalamotomy for Parkinson’s disease: microelectrode technique. In: Lunsford, L.D. (Ed.), Modern Stereotactic Neurosurgery, Nijhoff, Boston, MA, pp. 297~ 3 14. Schaltenbrand, G. and Wahren, W. ( 1977) Atlas for Stereotaxy of the Human Brain. Georg Thieme, Stuttgart. Laitinen, L.V. (1985) Brain targets in surgery for Parkinson’s disease. Results of a survey of neurosurgeons. J. Neurosurg. 62: 349935 1. Birk, P., Struppler, A., Lipinski, H.G., Giorgi. C., Cerchiari, U. and Riescher. H. (1987) Computer-assisted analysis of functional anatomy of human ventrolateral thalamus. Acta Neurochir., Suppl. 39: 57-60. Ojemann, G.A. (1985) Enhancement of memory with human ventrolateral stimulation: effect evident on a dichotic listening task. Appl. Neurophysiol., 48: 212-215. Hugdahl, K., Wester, K. and Asbjornsen, A. (1990) The role of the left and right thalamus in language asymmetry: dichotic listening in parkinsonian patients undergoing stereotactic thalamotomy. Brain Lang., 39: I--l 3. Rafal, R.D. and Posner, M.I. (1987) Deficits in human visual spatial attention following thalamic lesions. Proc. Natl. Acad. Sci. USA, 84: 7349-7353. Velasco, F., Velasco. M.. Ogarrio. C. and Olvera. A. (1986) Neglect induced by thalamotomy in humans: a quantitative appraisal of the sensory and motor deficits. Neurosurgery, 19: 744-750. Wester, K. (1971) Habituation to electrical stimulation of the thalamus in unanaesthetized cats. Electroenceph. Clin. Neurophysiol. 30: 52.-6 1. Wester. K. and Sagvolden, T. (1972) The thalamically induced orienting response in chronic cats with mesodiencephalic lesions. Brain Res.. 45: 383 392.
CliniculNeurologycmdNeurosurgery.94 (I 992) 25-30 0 1992Elsevier Science Publishers B.V. All rights reserved 0303-8467/92/$05.00
CLINEU
00179
The prognostic value of intra-operative observations during thalamotomy for parkinsonian tremor K. Wester” and E. Hauglie-Hanssenb Departments of Neurosurger.v, “Haukeland Sykehus, University of Bergen Medical School, Bergen, Norway, and bRikshospitalet, University of Oslo Medical School, Oslo, Norway (Received (Revised,
(Accepted
Key words:
Brain stimulation;
Parkinson’s
disease;
19 March,
1991)
received 29 July, 1991) 26 August,
Stereotaxic
1991)
techniques;
Thalamotomy;
Tremor
Summary Data from 27 thalamotomies observations and the long-term electrodes
in the target
threshold
intensities
were analyzed with respect to possible correlations between certain intra-operative effect on parkinsonian tremor. Tremor reduction caused by mechanical impact of the
area was not correlated
during
the intra-operative
with the long-term electrical
stimulation
effect on the tremor. of the target
The same was true for the
area,
stimulation
that
facilitates
and/or inhibits the tremor. In a minority of the patients, all with good long-term results, a combination of a pronounced tremor inhibition from the electrode insertion and a low threshold intensity was observed. Variations in other lesion parameters were not correlated with the outcome. The results are discussed within the framework of a “tremor” vs. a “tonus” mechanism underlying the thalamotomy effect.
Introduction
most effective target area in a possible tremorogenic tremor-mediating part of the diencephalon.
Stereotaxic thalamotomy is a well established symptomatic treatment for parkinsonian tremor and other
An acute oedema surrounding the lesion may attribute to the immediate inhibitory effect on tremor by tempo-
movement
rarily blocking
disorders.
The majority
of patients
resistant parkinsonian tremor benefit tion [l-13]. In a few cases, however,
with drug-
from this operathe tremor may
neural elements
gradually be reactivated, tremor. The postoperative
permanent tremor relief. The cause of the tremor
1). Provided
is not
known. However, it seems reasonable to suspect the lesion to have been too small and/or placed outside the
Correspondenceto: Dr. Knut Wester, Department Haukeland
Sykehus,
N-5021 Bergen. Norway.
of Neurosurgery,
in tremor
mech-
anisms. As the oedema subsides and natural repair processes take place, parts of the tremor mechanisms may
eventually reappear. This may happen also after excellent immediate results, in spite of apparently identical operative procedures as those performed in cases with relapse in these patients
involved
or
sive compared
causing reappearance oedema can be rather
with the volume
the concept
of the lesion proper
of a tremorogenic
thalamic
of the exten(Fig. area
is of some validity, one would expect this to be reflected in intra-operative observations. Although seldom discussed in scientific reports, most neurosurgeons performing thalamotomy probably assume this to be the case. As few have access to refined neurophysiological recording techniques [ 14-201, peroperative stimulation studies is the most common method for physiological
26
Fig. 1. Horizontal CT scans showing the maximal extent of the thalamic lesion 1 day (left) and 4 months (right) postoperatively. Note
the oedematous zone surrounding the inner core of the lesion.
target confirmation. Electrical stimulation of the target area may have dramatic effects on tremor (Fig. 2), and the threshold intensity for eliciting these effects can be determined (Fig. 3). Low threshold intensities are logically considered to indicate proximity to the optimal target area, and should therefore predict a successful lesion. When the electrodes are inserted into the target area, reduction or arrest of tremor is often observed (Fig. 4). This is presumably due to mechanical impact on neural elements, and is regarded as another promising sign, indicating a good long-term result. In the present study, we have analyzed whether these effects or other peroperative factors could be attributed to any prognostic significance for the final outcome of the operation.
larger sample of patients described elsewhere [I 31. Only those who had been operated on under standardized intra-operative conditions were selected. One patient was operated twice due to reappearance of the tremor; thus the total number of operations included was 27. Surgery
A detailed account for the surgical procedures is given elsewhere [13]. The thalamic target was located 2 mm behind the mid-commissural plane, 3 mm above the inter-commissural line and, most commonly, 14 mm laterally from the mid-sagittal plane. Two electrodes were used, 6 mm apart, the active tips measuring 2 mm. The inter-electrode plane was approximately parallel to the internal capsule. With the pre-selected target area, stimulation and lesioning was assumed to affect the ventrooral (v.o.a. and v.0.p.) and the reticular thalamic nuclei
VI. Material and methods
The lesions were calculated to be of the same size as those reported by Hirai et al. [6].
Patients
Twenty-six patients with parkinsonian tremor (age 49-73 years, median 64) were selected from a slightly
Recording
The tremor was recorded continuously
by means of
27
Fig. 2. Polygraph recordings showing effects of stimulation in the left thalamus on tremor in the contralateral (right) index finger. Stimulation parameters: 1.O mA, 50 Hz, 1.O msec. Upper trace: Time in set with stimulus marker (horizontal bar). Middle trace: left index finger (no tremor). Lower trace: right index finger. Left: arrest of ongoing tremor at the onset of stimulation. of tremor when stimulating with the same parameters against a background of no tremor.
mechano-electrical transducers mounted of both index fingers (see Figs. Z-4). Stimdution Prior to lesioning,
on the dorsum
the target area was screened
larily from a constant-current
stimulator
or (4) absent. In the final evaluation,
were grouped together as “good” results.
as “poor”
(1) and (2)
results, and (3) and (4)
for ef-
fects on tremor as well as for unwanted side effects by electrical stimulation. The stimulus was delivered bipopulses, pulse width
present,
Right: initiation
(50 Hz biphasic
1.O msec).
Results The present
paper deals only with the effect of the tha-
lamotomy on the tremor per se. According to the criteria given above, 5 of the operations were found to have
Ewluation of long-term t@cts All the patients were re-admitted
to our department
given “poor”, and 22 “good” results. This corresponds exactly with our own evaluation at the post-operative
for a 3-month post-operative control. However, to avoid possible bias on the authors’ part, the final evaluation was left to the patients’ referring neurological depart-
control
3 months
IZfjxt
qf’elrctrode
ment
(median 17) months (see ref. 13 for details). Among other questions, they were asked to indicate
In 14 operations, insertion of the electrodes into the target area caused a pronounced reduction of the tremor, i.e. an amplitude reduction of 50% or more. lasting for
whether the tremor, at the most recent visit, was (1) prc~mt (It ,fklI strength. (2) nlodwate!)~ presrnt, (3) slight!\,
minutes (Fig. 4). In a few cases, the tremor was almost abolished for the rest of the operation. In the remaining
after
_- ,--.%._ W-_-S_
a post-operative
observation
time
of 3-31
-....-q~.----I_
._-.--
after surgery. insertion
-.
------__a..----.
Fig. 3. Example of determination of threshold intensity. Same patient and stimulation parameters as in Fig. 2. Horizontal bars indicate thalamic stimulation with the following intensities (in mA, from left to right): 0.60. 0.55. 0.60. 0.80. 0.90. Note also the decreasing latencies with increasing stimulus intensities.
*_., -- ._ ._ A
-
-A
Fig. 4. Marked reduction of tremor in the left index finger (lower trace) induced by mechanical insertion (between arrows) of the electrodes from the cortical surface into the target in the right thalamus. Due to higher amplitude of the left-sided tremor, the gain in this trace is reduced 5-fold.
13 operations,
this effect was not convincingly observed, or it was less pronounced. In the analyses below, this mechanical effect was accordingly classified as being “pronounced” or “weak or absent”. The 2 result groups (“good” and “poor”) did not differ with respect to the presence or absence of mechanical insertion effect (Table 1).
and “poor”) did not differ significantly. either when tested on a ranking scale (Mann-Whitney U-test). or when tested with the Fischer exact probability test (Table 2). The combination of mechanical insertion ejfect and loo. threshold intensity In a minority of the operations, a pronounced mechanical insertion effect and a low threshold were both observed. All these operations had good long-term results (Table 3). This correlation approaches the level of statistical significance (x2 = 3.25, P = 0.07).
Stimulation effkcts Electrical stimulation of the ventrolateral thalamus most often had a dichotomic effect on the contralateral tremor. With the hands resting comfortably, stimulation most often elicited a typical parkinsonian tremor. When stimulating against a background of positional tremor, obtained by asking the patient to elevate his arms, identical stimulation could cause a prompt arrest of tremor (Fig. 2). The threshold intensities for eliciting these effects were found to vary between 0.5 and 2.0 mA, with a median of 1.25 mA. Threshold intensities below or above this median were classified as being “low” or “high”, respectively. Threshold intensities for the 2 result groups (“good”
Other factors The long-term results did not correlate with parameters relating to the size of the lesion (maximal heating time, temperature or total extent of the lesioned area).
TABLE I
TABLE 2
TREMOR-REDUCING EFFECT OF ELECTRODE INSERTION IN THE TARGET AREA VS. LONG-TERM EFFECT OF THE OPERATION -
THRESHOLD INTENSITIES FOR STIMULATION EFFECTS ON TREMOR VS. LONG-TERM EFFECT OF THE OPERATION
Insertion effect
Threshold intensity
Long-term effect of the operation Good
Poor
Pronounced Weak or none
12 9
2 4
Total
21
6
Discussion Although not commonly mentioned in the literature, it
Long-term effect of the operation Good
Poor
Low High
12 9
2 4
Total
21
6
29 TABLE 3
lesions for a wide variety of dyskinesias
COMBINED FACTORS (EFFECT OF ELECTRODE SERTION AND LOW THRESHOLD INTENSITIES) LONG-TERM EFFECT OF THE OPERATION
INVS.
understand
targets
ful targets
21
6
although thalamic
mal movements
subdivision
neurosurgeons
perform-
ing thalamotomies that substantial tremor reduction, when the electrode is inserted into the target, is a good omen, as it is when electrical stimulation of the target affects tremor
even at low intensities.
these assumptions tremorogenic or
The logic behind
must be that there exists a restricted tremor-mediating diencephalic area,
and that the effect of the operation lesion is to this area.
to
throughout has yet been
clinical
targets.
can alleviate character
in different
abnor-
and etiol-
parts of this digood effects
These facts are difficult
of a restricted
on Use-
to ex-
and specific tremor
mechanism. The present
among
widely
seem to have equally
tremor.
plain by the existence
opinion
operations.
no attempt lesions
of different
on parkinsonian
,$ = 3.25. P = 0.01.
is a wide-spread
scattered
ogy, and vice versa: lesions encephalic
of symptoms. Laitinen’s [22] survey
the results of using different
identical
to the
in a specific tremor mechanism
are apparently
the diencephalon, Thus,
in addition
[I 31. It is difficult
for tremor-alleviating
made to compare 0 6
and rigidity
how lesions
preferred
Poor
Low threshold und pronounced insertion 8 effect 13 Other operations Total
tremor
should alleviate such a variety More doubt emerges from
Long-term effect of the operation Good
parkinsonian
is better the closer the
The concept of a restricted tremorogenic area receives support from the electrophysiological works of AlbeFessard [14], Jasper [16], Ohye [18,19] and others [17,20]. In his microelectrode studies, Ohye has demonstrated thalamic (Vim) cells that fire in a synchronous fashion
results, especially
those from the stimula-
tion studies, are similarly difficult to explain within the concept of such a mechanism. To us, the presently available data seem to favour some sort of “tonus” rather than a “tremor” mechanism theory. Such a tonus mechanism may possibly play on the muscular tone [23]. There is also evidence that this part of the thalamus may play some part in the attentional tone [24-291. The proximity of the target
area
such as the reticular this context.
to non-specific nucleus,
thalamic
is of particular
structures, interest
in
The prognostic value of the intra-operative observations described here seems to be of limited importance. One can relatively safely predict a good long-term outcome if a pronounced insertion effect and a low threshold intensity appear in combination. However, excellent re-
with the tremor. These cells are located in the same thalamic subdivision, or even within the same nucleus where
sults may occur without
lesions can alleviate tremor. It is therefore possible that these cells “are involved in the tremor-mediating system.
Acknowledgements
if not in the tremor genesis” [18]. However, such observations cannot be taken as evidence for a causal relation-
The authors wish to thank professor E.-O. Backlund for his invaluable criticism and comments, and Dr. M.
ship between
Lund-Johansen
the two phenomena,
with the thalamic
unit
firing being the primary event. On the contrary, it may well be that the thalamic cell activity is merely reflecting the peripheral muscle activity associated with the tremor, thus being a secondary event. Ohye has himself demonstrated that such units can be driven by stretching muscles
involved
in the tremor
[18].
There are also intriguing facts that undermine the notion of a restricted tremorogenic area in the thalamus. Lesions in the same area can alleviate a number of different movement disorders. also when tremor is not involved [20]. We have ourselves used identical thalamic
this combination.
for technical
assistance.
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