Corpus callosotomy effects on cerebral blood flow and evoked potentials (transcallosal diaschisis)

Neuroscience Letters, 154 (1993) 9-12 © 1993 ElsevierScientificPublishers Ireland Ltd. All rights reserved0304-3940/93/$06.00

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Corpus callosotomy effects on cerebral blood flow and evoked potentials (transcallosal diaschisis) Russell J. A n d r e w s a'c, J o h n R. Bringas a'c, G i n a A l o n z o a'~, M. S h a h r i a r S a l a m a t b, Sami K h o s h y o m n a'c a n d D a n i e l S. G l u c k a'c Departments ofaNeurological Surgery and bPathology ( Neuropathology ), University of California at Davis, Medical Center, Davis (USA.) and cVeterans Affairs Medical Center, Martinez, CA (USA)

(Received 12 November 1992; Revisedversion received 19 January 1993;Accepted 21 January 1993) Key words: Brainretraction; Cerebral blood flow; Corpus callosum; Diaschisis; Evoked potentials; Focal cerebral ischemia

The role of the corpus callosum in diaschisis was examinedthrough the acute effectsof stereotacticcorpus callosumsectionon cerebralblood flow and somatosensoryor auditory evoked potentials bilaterallyduring unilateral brain retraction ischemia, using a previouslyreported swine model. Cerebral blood flowand evokedpotential amplitudecontralateral to retraction increasedduring retraction with the corpus callosumintact, compared with post-callosal section values. With retraction following callosat section, there was no increase in cerebral blood flow or evoked potential amplitude contralateral to retraction. Diaschisis during the early stages of a focal, unilateral injury takes the form of a contralateral disinhibition (as measured by cerebral blood flowand evoked potentials), an effectwhich is lost followingcallosal section.

The term 'diaschisis' was first used by von Monakow in 1914 to describe distant changes in the nervous system following a focal injury [15]. He emphasized the importance of neural connections: '...diaschisis represents an 'interruption of function' appearing in most cases quite suddenly.., which originates from a local lesion but has its points of impact...only at points where fibres coming from the injured area enter intact grey matter...' [15]. Most studies of diaschisis have considered distant effects hours or days after an insult (e.g. middle cerebral artery stroke) rather than during the initial stages [7, 12]. In our review of transhemispheric diaschisis, we found that the contralateral effects of a focal injury depended on the time after the injury at which the diaschisis was assessed [11. In our previously-described large animal model simulating operating room brain retraction ischemia [2, 3], we noted changes in the contralateral hemisphere during unilateral retraction [4]. There was an increase in cerebral blood flow (CBF) and evoked potential (EP) amplitude contralateral to retraction. Given the abundant transcallosal connections between the somatosensory and auditory cortices, we have repeated our unilateral Correspondence: R.J. Andrews. Present address: VA Medical Center (Neurosurgery 112D), 3801 Miranda Avenue, Palo Alto, CA 94304, USA. Fax: (1) (415) 852-3430.

retraction protocol with the corpus callosum sectioned in order to assess the importance of transcallosal connections to the contralateral CBF and EP changes during focal unilateral ischemia. The animal model and techniques have been described elsewhere in detail [2, 3]; only a brief summary is provided here. Eleven juvenile domestic swine (10 to 35 kg) were used. Following intramuscular injection of atropine sulfate (0.05 mg/kg) and fentanyl (0.4 mg/15 kg) plus droperidol (20 mg/15 kg) (Innovar-Vet 1 ml/15 kg), endotracheal intubation was performed, and femoral arterial and venous access established by cutdown. Maintenance anesthesia was isoflurane 1.5 to 2%. ThepCO2 was maintained at 40 mmHg. At the completion of the experiment (10 to 12 h of retraction-recovery recording sequences), the animal was sacrificed by pentobarbital overdose. The head was placed in a stereotactic holder, and a wide bilateral craniectomy was performed as described previously [3]. The corpus callosum was sectioned approximately one-half way through the recording period for each animal, to give similar numbers of retractionrelease sequences both pre- and post-callosal sectioning. The stereotactic callosotomy technique described by Magni [10] and Fukuda [8] was employed. A 2-mm incision was made in the dura approximately 2 mm lateral to the midline at a point 2 cm posterior to the frontal poles.

A similar incision was made on the same side 4 cm posterior to the first incision. A fine wire with a 3-0 suture attached to the tip (by bending the wire back on itself) was passed from the anterior dural incision to the posterior incision, sliding the rounded tip of the wire along the inner surface of the parasagittal dura. The suture was threaded through two straight needles attached to stereotactic towers placed so as to lower the needles through the two incisions in the dura. The needles were lowered to a depth of 2.5 cm. The corpus callosum was then sectioned by pulling on the two ends of the suture with a gentle sawing motion. No acute changes in blood pressure or E K G were seen at this time. To confirm the callosal section, the brain was removed immediately after sacrifice and placed in formalin. Each of the 11 brains was later sectioned coronally at 5-mm intervals and reviewed by a neuropathologist (MSS). To measure brain retraction pressure, the strain gauge attached to a 0.25-inch brain retractor blade employed previously was again held by a stereotactic tower to retract either subfrontally or subtemporally [3, 4]. Forelimb somatosensory EP (SEE for subfrontal retraction) and auditory EP (AER for subtemporal retraction) were mapped bilaterally using silastic/stainless steel strip electrodes (four electrodes at 5-mm spacing), as described previously [2]. The EPs were collected (a) baseline (sum of 250 for SEE sum of 125 for AEP), (b) every 5 min during retraction until the EP amplitude in the electrode with the largest baseline amplitude had decreased 50% or a total of 30 min of retraction was reached, and (c) at 5 rain and 10 rain post-retraction. Laser-Doppler focal cortical cerebral blood flow (CBF) was measured with the Laserflo BPM-403A Blood Perfusion Monitor (Vasamedics, Inc., St. Paul, MN). Needle point probes (0.8 mm diameter) connected to stereotactic towers were placed to lightly contact the cortical surface (epidurally) immediately medial to the electrode of the strip array with the highest EP amplitude bilaterally. Because the somatosensory cortex is more medial than the auditory cortex, the probes were placed immediately lateral - rather than medial - to the electrode with maximal EP amplitude during SEP recording [3, 4]. Care was taken that the probes did not move during or between recordings, and that they were not placed over a superficial vessel (which would result in increased CBF readings). The callosal section included the body of the corpus callosum in all cases, which therefore included the somatosensory and auditory catlosal fibers [14]. In three brains the anterior 2 to 3 mm of the corpus catlosum was not sectioned; in one brain the posterior 2 mm was not sectioned. Slight diencephalic penetration was appreciated in three brains. Mild subarachnoid and/or intraven-

tricular hemorrhage was common, but the contribution of brain removal (rather than the callosal sectioning) to these hemorrhages is uncertain. The paired t-test for the difference between means was used to assess changes in MAR pC02, and CBF (Table 1) [5]. For comparisons of contralateral CBF and EP before and after corpus callosotomy (Table 2), the values were converted from ml/100 g/min or ¢tV to a percentage of baseline values. Of the 50 retraction-recovery sequences with the corpus callosum intact, AEPs were recorded in 22 and SEPs in 28. Of the 51 retraction-recovery sequences with the corpus callosum sectioned, AEPs were recorded in 22 and SEPs in 29. Data on blood pressure (MAP), pCO2, and bilateral CBF before and after callosal section are given in Table I. There was a trend to lower MAP after callosal section (P --~ 0.06), and a relatively small (14%) but statistically significant (P ~ 0.003) decrease in CBF following corpus callosum section. The CBF and EP values contralateral to the retraction, both before and after callosal sectioning, are given in Table 2 as a percentage of the corresponding baseline values. For both CBF and EP, the contralateral mean value was significantly lower with the corpus callosum sectioned than with it intact ( P < 0.00001 and P ~ 0.0015, respectively). The two principal findings are (1) that callosal section alone resulted in a mild (14%) but highly statistically significant decrease in CBF, and a smaller (5%), marginally significant, decrease in MAP; and (2) that the increase in CBF and EP amplitude (20% and 9%, respectively) seen contralaterally during unilateral retraction ischemia was lost following callosal section: in fact, a decrease was seen contralaterally in both CBF and EP amplitude (7% and 15%, respectively). Baseline qffects of callosal section. Some previous reports of callosal section do not observe CBF changes attributable to the sectioning itself [11, 13]. Others have TABLE 1 MEAN ARTERIAL BLOOD PRESSURE, pCO 2, A N D CEREBRAL BLOOD FLOW BEFORE A N D A F T E R CORPUS CALLOSUM SECTION Number, number of retraction-recovery sequences: MAP, mean arterial blood pressure; CBK cerebral blood flow (bilateral). Values are mean ± standard deviation.

N umber MAP(mmHg) pCO2 (mmHg) CBF (ml/100 g/min)

Corpus callosum intact

Corpus callosum p-value sectioned

5(I 66.3± 9.7 39.6 ± 5.2 45.9 + 10.3

51 63.1 _+ 7.5 40.5 ± 5.1 39.7 ± 10.4

~0.06 ~ 0.35 ~ 0.003

11 noted a bilateral depression in cortical metabolism (as measured by 18F-fluorodeoxyglucose positron emission tomography) following callosal sectioning, at least in later time periods (1 to 3 weeks post-section) [17]. However, our CBF and M A P values were obtained over the first 5 h following callosal section. This is more acute than previous data, and m a y explain the discrepancy. It is unlikely that the CBF decrease (14%) can be fully attributed to the much smaller M A P decrease (5%). With regard to electrical activity, we are not aware of data regarding whether callosal section in itself has any significant effect on the amplitude of hemispheric electrical activity (spontaneous or evoked). Corpus callosum section does, however, reduce or abolish the synchrony of electrical activity between the two hemispheres. Examples involving the visual system are (1) the loss of ipsilateral (but not contralateral) E E G seizures with monocular intermittent light stimulation in the epileptic baboon following callosal section [8], and (2) the loss of interhemispheric synchronization of oscillatory neuronal responses in the cat visual cortex following callosal section [6]. Diaschisis effects of callosal section. During unilateral focal retraction ischemia, there is an increase in the contralateral CBF and SEP or AEP amplitude. Sectioning the corpus callosum results in a loss of this contralateral increase. Few other studies have examined what we have termed 'the hyperacute stage of transhemispheric diaschisis' or first hour of focal ischemia [1]. Meyer et al. [11] found a period of contralateral 'reactive hyperemia' during the first 30 rain following unilateral embolic infarction in the baboon with corpus callosum intact. A progressive decline in contralateral CBF ensued over the first 7 days, followed by a gradual increase toward baseline levels. The effects of corpus callosum sectioning on diaschisis have been studied primarily at time periods later than the hyperacute stage. Meyer et al. [1 1] found that diaschisis, in terms of a change in contralateral CBF two or more TABLE II CEREBRAL BLOOD FLOW AND EVOKED POTENTIAL AMPLITUDE CONTRALATERAL TO RETRACTION ISCHEMIA BEFORE AND AFTER CORPUS CALLOSUM SECTION Number, number of retraction-recovery sequences; CBF, cerebral blood flow; EP, evoked potential amplitude. Values are mean _+standard deviation. Corpus callosum Corpus callosum p value intact sectioned Number 50 CBF (% of baseline) 120.4+ 26.0 EP (% of baseline) 108.8_+37.7

51 93.4 _+21.4 85.4 _+36.1

< 0.00001 ~ 0.0015

hours after unilateral embolization, was lost when the corpus callosum had been previously sectioned. The findings of Miller et al. [13] are similar in that corpus callosum sectioning in dogs resulted in a loss of the contralateral changes in CBF seen during unilateral ischemia with intact animals (middle cerebral artery occlusion model). Yamaguchi et al. [16] found that corpus callosum sectioning influenced the rate of recovery of glucose metabolism following unilateral lesioning of the nucleus basalis of Meynert. Unilateral lesioning (with an intact corpus callosum) resulted in bilateral reduction in glucose metabolism, with nearly complete recovery over the following 39 days [16]. Recovery was only minimal, however, at 39 days post-lesioning in callosal-section animals. Conclusions. The corpus callosum plays an important role in transhemispheric diaschisis. This diaschisis takes the form of a contralateral disinhibition or facilitation in the very early stage. Later, the diaschisis results in a contralateral depression (which gradually resolves after weeks to months in man) [1]. The contralateral increase in CBF and EP amplitude seen during unilateral focal ischemia with an intact corpus callosum is lost following callosal section. Serial measurements of CBF, electrical activity, and/or cerebral metabolism in the same model following callosal section will detail the transition from the acute phase where transcallosal diaschisis is disinhibitory to the somewhat later period when transcallosal diaschisis is inhibitory. We thank Drs. David Woods and Robert Knight of the UC Davis East Bay Neurology Program for their advice and comments, Howard Menche, Jr., of the NASA-Ames Research Center for fabricating the strain gauge retractor, and Anaquest, Inc., Madison, WI, for providing much of the isoflurane anesthetic used in these experiments. This research was funded in part by a VA Merit Review grant. 1 Andrews, R.J., Transhemisphericdiaschisis: a reviewand comment, Stroke, 22 (1991) 943 949. 2 Andrews, R.J., Knight, R.T. and Kirby, R.P., Evoked potential mapping of auditory and somatosensory cortices in lhe miniature swine, Neurosci. Lett., 114 (1990) 27 31. 3 Andrews, R.J. and Muto, R.E, Retraction brain ischemia: hypotension, hyperventialation, and age effects on evoked potentials and cerebral blood flow in an animal model, Neurol. Res., 13 (1992) 12-18. 4 Andrews, R.J. and Muto, R.E, Retraction brain ischemia: mannitol and nimodipine preserves both cerebral blood flow and evoked potentials during normoventilation and hyperventilation, Neurol. Res., 13 (1992) 19-25. 5 Armilage, P., Statistical Methods in Medical Research, John Wiley, New York, 1971, 504 pp. 6 Engel, A.K., Konig, E, Kreiter, A.K. and Singer, W., Interhem-

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