Journal of Neurosurgical Anesthesiology Vol. 14, No. 4, pp. 299–303 © 2002 Lippincott Williams & Wilkins, Inc., Philadelphia Interhemispheric Intracranial Pressure Gradients in Massive Cerebral Infarction *J. Ricardo Carhuapoma, †Adnan I. Qureshi, †Anish Bhardwaj, and †Michael A. Williams *Neurosciences Critical Care Program, Wayne State University School of Medicine, Detroit, Michigan; and †Division of Neurosciences Critical Care, The Johns Hopkins University School of Medicine, Baltimore, Maryland Summary: We report continuous bilateral intracranial pressure (ICP) monitoring immediately after transtentorial herniation in a patient with massive cerebral infarction to: 1) determine presence and time course of compartmental ICP differences, and 2) to study effects of therapy on both hemispheres. A 55-year-old man admitted with watershed infarctions in the left anterior-middle-posterior cerebral arteries distribution. Initial investigations demonstrated highly narrowed left extracranial internal carotid artery. Eight days later he developed unexplained lethargy and anisocoria. Head computerized tomography (CT) showed massive left hemispheric infarction, edema, and midline shift. Bilateral subarachnoid bolts demonstrated equally elevated ICP in both hemispheres. Hyperventilation and osmotic therapy produced near-identical ICP reduction bilaterally with resolution of anisocoria. Later, plateau waves and autonomic instability developed. Shortly before loss of brainstem function, interhemispheric ICP gradients (left greater than right) of 30–40 mm Hg developed. Intracranial pressure did not equalize prior to brain death determination. Bilateral ICP monitoring did not reveal an interhemispheric ICP gradient soon after transtentorial herniation in massive MCA infarction. The presence of interhemispheric ICP gradients in massive stroke remains unproven and further clinical study is necessary. Key Words: ICP—Hyperventilation—Osmotic therapy— Brain edema The presence of compartmental intracranial pressure (ICP) gradients has been a subject of debate for several decades in neurosciences (1–3). Most of the experience in this field originates from traumatic brain injury patients. Attempts to improve our understanding of ICP gradients have included unihemispheric and bihemispheric ICP monitoring in patients with diffuse brain swelling or unilateral mass lesions. However, their presence in massive ischemic stroke as a cause of neurologic deterioration has never been documented. Ropper proposed that worsening level of consciousness in acute unilateral mass lesions correlates with the horizontal shift of structures involved in the physiology of consciousness and arousal (4). This notion could have significant therapeutic implications when applied to patients with cerebrovascular disease, because current standards in treatment of elevated ICP rely on preservation of cerebrovascular physiologic properties. Because they may be absent in ischemic brain regions, ICP treatment modalities could have preferential effects on normal tissue, accentuate any preexisting ICP gradient, worsen shift, and further neurologic deterioration. Address correspondence and reprint requests to Dr. J. Ricardo Carhuapoma, Neurosciences Critical Care Program, Wayne State University School of Medicine, University Health Center, 8C, 4201 St. Antoine Boulevard, Detroit MI 48201. Accepted for publication on April 24, 2002. Dr. Carhuapoma is supported in part by the David A. Dana Research Prize in Neurosciences Critical Care, Johns Hopkins University School of Medicine and the Daland Fellowship Award from the American Philosophical Society. Dr. Bhardwaj is supported in part by the Clinician Scientist Award from the American Heart Association. 299 DOI: 10.1097/01.ANA.0000027069.13775.31 300 J. R. CARHUAPOMA ET AL. left ICA C1 segment velocity (171 cm/sec) and delayed systolic upstroke and decreased cerebral blood flow velocities in the M1 (21 cm/sec) and M2 (13 cm/sec) segments of the left MCA, suggesting superimposed highgrade stenosis of the left ICA C1 segment. Therapies at this point consisted of mechanical ventilation due to COPD exacerbation, intravenous hydration with iso-osmolar fluids, and aspirin 325 mg daily for secondary stroke prevention. He remained neurologically stable until 8 days later, when unexpectedly obtundation and anisocoria developed acutely. An emergent head CT showed early evidence of massive left hemispheric infarction with associated mass effect and midline shift (Fig. 2). Follow-up TCD investigation demonstrated bidirectional blood flow in the left ophthalmic artery associated with significantly reduced pulsatility index (PI). No audible signal could be obtained from the left ICA C3 (intracavernous) segment, suggesting superimposed left ICA C3 segment occlusion. Hyperosmolar therapy and hyperventilation were immediately instituted, and bilateral subarachnoid bolts (Codman & Shurtleff, Randolph, MA) FIG. 1. Head CT scan obtained at the time of admission showing discrete left watershed infarctions between the territories of the ACA, MCA, and PCA, without evidence of mass effect or shift of the midline structures. We report continuous, bilateral ICP monitoring soon after transtentorial herniation in a patient with massive hemispheric cerebral infarction, describe the presence and time course of compartmental ICP differences, and discuss probable effects of therapy on both healthy and infarcted hemispheres during this process. CASE REPORT A 55-year-old man developed acute right hemiparesis, dysarthria, and left gaze preference. He was a smoker and suffered from hypertension, diabetes mellitus, and severe chronic obstructive pulmonary disease (COPD). Rather than a territorial hemispheric infarction, initial head CT revealed discrete, small watershed infarctions in the distribution of the left anterior, middle, and posterior cerebral arteries (Fig. 1). Early endotracheal intubation and mechanical ventilation were required for treatment of COPD worsening. Doppler investigation of the extracranial internal carotid artery (ICA) revealed severely narrowed left ICA. Transcranial Doppler (TCD) study revealed elevated Journal of Neurosurgical Anesthesiology, Vol. 14, No. 4, 2002 FIG. 2. Head CT scan obtained at the time of herniation showing evidence of extensive left hemispheric infarction associated with severe edema, producing mass effect, significant midline structures shift, and entrapment of the right lateral ventricle’s occipital horn. ICP, CEREBRAL INFARCTION, BRAIN EDEMA were placed to monitor ICP and its response to therapy. From the time these fluid-coupled devices were placed, equally elevated ICP (mean of 40 mmHg) with symmetric waveform morphology was recorded in both hemispheres. Hyperventilation and osmotic therapy with 25% mannitol and 2% sodium chloride/acetate solution were begun, resulting in PaCO2 of 34 mmHg and serum sodium concentration of 160 mEq/L. Near identical ICP reduction from 40 to 15 mmHg in both hemispheres was followed by resolution of anisocoria (Fig. 3), but without improvement in the level of consciousness. Despite continuous administration of hypertonic saline to maintain serum sodium concentrations between 150 and 155 mEq/L, plateau waves and autonomic instability (supraventricular tachycardia) developed 12 hours later without additional neurologic deterioration. Approximately 4 hours before loss of brainstem function, an interhemispheric ICP gradient of 30 to 40 mmHg gradually developed (Fig. 4), with ICP higher on the left. At this point, neurologic examination demonstrated bilateral flaccidity and absent corneal and cough reflexes. Both pupils were 2 to 2.5 mm in diameter and poorly responsive to light. While on synchronized intermittent mechanical ventilation at a rate of 14 breaths per minute, and with PaCO2 of 30 mmHg, the patient’s spontaneous respirations gradually became shallow and irregular during the following hours. Transcranial Doppler showed only short systolic spikes throughout the right hemisphere and posterior circulation, consistent with severely increased ICP and circulatory arrest in the cerebral vasculature on the right. No audible signal was obtained 301 on the left side. The interhemispheric ICP gradient did not resolve prior to brain death determination. Discussion The case we report documents near-identical bihemispheric ICP pressures measured immediately after transtentorial herniation and suggests that the process of herniation after massive MCA infarction may not be necessarily the result of interhemispheric ICP differences. Furthermore, emergency treatment of ICP with hyperventilation and osmotic agents neither created interhemispheric ICP differences, nor did it worsen neurologic function, although the patient ultimately died of refractory cerebral edema and asymmetric ICP elevation. Hacke et al. have described development of malignant cerebral edema after massive hemispheric cerebral infarction and the associated ICP elevation that follows (5). Although elevated ICP can clearly worsen outcome or cause death after stroke, indications for ICP monitoring after hemispheric infarction remain ill defined. In the treatment of patients with massive ischemic stroke, Schwab et al. concluded that high ICP predicted poor response to medical treatment and poor survival; however, its monitoring did not alter neurologic outcome (6,7). Nevertheless, in certain settings, only ICP monitoring allows us to assess response to therapy and to recognize progression of brain edema. Induced hypothermia and decompressive hemicraniectomy are two potential therapeutic options for the treatment of malignant brain edema associated with hemispheric stroke that require ICP moni- FIG. 3. Intracranial pressure response to the administration of osmotic therapy (2% sodium chloride/acetate) and hyperventilation, as measured by bilateral subarachnoid bolts. Journal of Neurosurgical Anesthesiology, Vol. 14, No. 4, 2002 302 J. R. CARHUAPOMA ET AL. FIG. 4. Refractory interhemispheric ICP gradient before loss of brainstem function. toring for their implementation (6,8–12). Whether additional patients with ischemic cerebrovascular disease may benefit from ICP monitoring remains unclear at this time, and the decision to monitor ICP must still be made on an individual basis. In 1995, Frank postulated that neurologic deterioration following acute ischemic stroke is probably the result of horizontal tissue shift, rather than secondary to “globally” elevated ICP (13). Further confirmation of the role of regional tissue shifts in this pathologic process was initially provided by investigations using head CT image analysis and later by sequential coronal MRI studies in patients with acute hemispheric mass lesions (4,14). Together, these observations support the notion that neurologic deterioration after brain injury with unilateral mass lesions may result from local pressure gradients leading to distortion, dysfunction, and compression of nearby anatomic structures related to consciousness (15–18). Because hyperventilation and osmotic therapy exert their therapeutic effects through preserved physiologic mechanisms in uninjured brain regions, their use in patients with brain edema after hemispheric infarction has generated concerns (19–23). If brain volume reduction is preferentially achieved in areas with preserved physiologic response to hypocarbia and osmotic gradient generation, hyperventilation and osmotic therapy could conceivably worsen preexisting horizontal tissue shifts and further subsequent neurologic deterioration. Contrary to this concept, our patient showed similar ICP response to hyperventilation and osmotic therapy in both hemispheres. It was only shortly before the loss of brainstem reflexes, presumably when brain edema reached its maximum in Journal of Neurosurgical Anesthesiology, Vol. 14, No. 4, 2002 the ischemic hemisphere, that an interhemispheric ICP gradient appeared despite antiedema treatment. We propose two potential explanations for such symmetric response: 1) although inconsistent with current understanding of CBF pathophysiology in acute stroke, areas of brain with preserved vasoreactivity and BBB integrity could have remained present in ischemic tissue, and thus had a similar response to hypocarbia and osmotic agents as the contralateral hemisphere producing equal ICP reduction; or more likely 2) the supratentorial compartment behaves as a single compartment and ICP changes are evenly distributed, at least during early stages. Clearly, we cannot fully exclude possible subarachnoid bolt malfunction preventing us from detecting existing ICP gradients. Nevertheless, we consider this unlikely on the basis of symmetric ICP waveform morphology, and symmetric, bilateral ICP response to physiologic maneuvers. 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