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Cerebral blood flow and metabolism in severely head-injured children

Part 1: Relationship with GCS score, outcome, ICP, and PVI

J. Paul Muizelaar, Anthony Marmarou, Antonio A. F. DeSalles, John D. Ward, Richard S. Zimmerman, Zhongchao Li, Sung C. Choi, and Harold F. Young

✓ The literature suggests that in children with severe head injury, cerebral hyperemia is common and related to high intracranial pressure (ICP). However, there are very few data on cerebral blood flow (CBF) after severe head injury in children. This paper presents 72 measurements of cerebral blood flow (“CBF15”), using the 133Xe inhalation method, with multiple detectors over both hemispheres in 32 children aged 3 to 18 years (mean 13.6 years) with severe closed head injury (average Glasgow Coma Scale (GCS) score 5.4). In 25 of the children, these were combined with measurements of arteriojugular venous oxygen difference (AVDO2) and of cerebral metabolic rate of oxygen (CMRO2). In 30 patients, the first measurement was taken approximately 12 hours postinjury. In 18 patients, an indication of brain stiffness was obtained by withdrawal and injection of ventricular cerebrospinal fluid and calculation of the pressure-volume index (PVI) of Marmarou. The CBF and CMRO2 data were correlated with the GCS score, outcome, ICP, and PVI.

Early after injury, CBF tended to be lower with lower GCS scores, but this was not statistically significant. This trend was reversed 24 hours postinjury, as significantly more hyperemic values were recorded the lower the GCS score, with the exception of the most severely injured patients (GCS score 3). In contrast, mean CMRO2 correlated positively with the GCS score and outcome throughout the course, but large standard deviations preclude making predictions based on CMRO2 measurements in individual patients. Early after injury, there was mild uncoupling between CBF and CMRO2 (CBF above metabolic demands, low AVDO2) and, after 24 hours, flow and metabolism were completely uncoupled with an extremely low AVDO2. Consistently reduced flow was found in only four patients; 28 patients (88%) showed hyperemia at some point in their course. This very high percentage of patients with hyperemia, combined with the lowest values of AVDO2 found in the literature, indicates that hyperemia or luxury perfusion is more prevalent in this group of patients. The three patients with consistently the highest CBF had consistently the lowest PVI: thus, the patients with the most severe hyperemia also had the stiffest brains. Nevertheless, and in contrast to previous reports, no correlation could be established between the course of ICP or PVI and the occurrence of hyperemia, nor was there a correlation between the levels of CBF and ICP at the time of the measurements. The authors argue that this lack of correlation is due to: 1) a definition of hyperemia that is too generous, and 2) the lack of a systematic relationship between CBF and cerebral blood volume. The implications of these findings for therapeutic modes of controlling ICP in children, such as hyperventilation and the use of mannitol, are discussed.

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Richard S. Zimmerman, Robert F. Spetzler, K. Stuart Lee, Joseph M. Zabramski, and Ronald W. Hargraves

✓ Once they become symptomatic, cavernous malformations of the brain stem appear to cause progressive morbidity from repetitive hemorrhage, and can even be fatal. Twenty-four patients with long-tract and/or cranial nerve findings from their cavernous malformations of the brain stem were seen for initial evaluation or surgical consultation and thereafter received either surgical or continued conservative treatment. The decision to operate was based on the proximity of the cavernous malformation to the pial surface of the brain stem, the patient's neurological status, and the number of symptomatic episodes. Sixteen patients were treated by definitive surgery directed at excision of their malformation. In four patients, associated venous malformations influenced the surgical approach and their recognition avoided the risk of inappropriate excision of the venous malformation. Although some of the 16 patients had transient, immediate, postoperative worsening of their neurological deficits, the outcome of all except one was the same or improved. Only one patient developed recurrent symptoms: a new deficit 2½ years after surgery required reoperation after regrowth of the cavernous malformation. She has been neurologically stable since the second surgery. One patient died 6 months postoperatively from a shunt infection and sepsis. The eight conservatively treated patients are followed with annual magnetic resonance imaging studies. One has a dramatic associated venous malformation. Seven patients have either minor intermittent or no symptoms, and the eighth died from a hemorrhage 1 year after his initial presentation.

Based on these results, surgical extirpation of symptomatic cavernous malformations of the brain stem appears to be the treatment of choice when a patient is symptomatic, the lesion is located superficially, and an operative approach can spare eloquent tissue. When cavernous malformations of the brain stem are completely excised, cure appears permanent.

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Joseph M. Zabramski, Robert F. Spetzler, K. Stuart Lee, Stephen M. Papadopoulos, Edwin Bovill, Richard S. Zimmerman, and Joshua B. Bederson

✓ Recent laboratory studies have demonstrated that intracisternal administration of recombinant tissue plasminogen activator (rt-PA) can facilitate the normal clearing of blood from the subarachnoid space and prevent or ameliorate delayed arterial spasm. The results of a preliminary Phase I trial of intracisternal rt-PA in 10 patients are reported with documented aneurysmal subarachnoid hemorrhage (SAH). All patients enrolled were classified as clinical Grade III or IV (according to Hunt and Hess) with thick clots or layers of blood in the basal cisterns and major cerebral fissures (Fisher Grade 3). Ventriculostomy and surgery for clipping of the aneurysms were performed within 48 hours of hemorrhage. In one patient, 10 mg rt-PA was instilled into the subarachnoid cisterns prior to closing the dura. In the remaining nine patients, a small silicone catheter was left in the subarachnoid space and rt-PA (5 mg in four cases or 1.5 mg (0.5 mg every 8 hours for three infusions) in five cases) was instilled 12 to 24 hours after surgery. Minor local bleeding complications were noted in all patients receiving 5 or 10 mg rt-PA. Oozing was noted at the operative incision site in four of five patients and at the ventriculostomy site in two patients. One patient developed a small epidural hematoma that was treated by delayed drainage. No bleeding complications were noted in the patients receiving the lower regimen of rt-PA (three infusions of 0.5 mg each). Serial coagulation studies demonstrated no evidence of systemic fibrinolysis. Analysis of cisternal cerebrospinal fluid samples revealed thrombolytic tissue plasminogen activator (t-PA) levels for 24 to 48 hours. Follow-up cerebral angiography 7 to 8 days after rupture disclosed mild to moderate spasm in nine patients, while one patient with hemorrhage from a posterior inferior cerebellar artery aneurysm had severe focal spasm of the vertebral arteries that was not symptomatic. These results suggest that postoperative treatment with rt-PA may be effective in reducing the severity of delayed cerebral vasospasm. The results of serial t-PA levels suggest that the lower dosage regimen with divided dosages at 8-hour intervals is well tolerated and that even lower dosages may be effective. Further studies are clearly indicated.

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Robert F. Spetzler, Ronald W. Hargraves, Patrick W. McCormick, Joseph M. Zabramski, Richard A. Flom, and Richard S. Zimmerman

✓ The relationship between the size of an arteriovenous malformation (AVM) and its propensity to hemorrhage is unclear. Although nidus volume increases geometrically with respect to AVM diameter, hemorrhages are at least as common, in small AVM's compared to large AVM's. The authors prospectively evaluated 92 AVM's for nidus size, hematoma size, and arterial feeding pressure to determine if these variables influence the tendency to hemorrhage.

Small AVM's (diameter ≤ 3 cm) presented with hemorrhage significantly more often (p < 0.001) than large AVM's (diameter > 6 cm), the incidence being 82% versus 21%. Intraoperative arterial pressures were recorded from the main feeding vessel(s) in 24 of the 92 patients in this series: 10 presented with hemorrhage and 14 presented with other neurological symptoms. In the AVM's that had hemorrhaged, the mean difference between mean arterial blood pressure and the feeding artery pressure was 6.5 mm Hg (range 2 to 15 mm Hg). In the AVM's that did not rupture, this difference was 40 mm Hg (range 17 to 63 mm Hg). Smaller AVM's had significantly higher feeding artery pressures (p < 0.05) than did larger AVM's, and they were associated with large hemorrhages. It is suggested that differences in arterial feeding pressure may be responsible for the observed relationship between the size of AVM's and the frequency and severity of hemorrhage.

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Brian C. Fitzpatrick, Robert F. Spetzler, Jeffrey L. Ballard, and Richard S. Zimmerman

✓ The technique for cervical-to-petrous internal carotid artery saphenous vein bypass is described. This procedure was used in the treatment of three patients with high cervical or skull base vascular injuries. All grafts were patent on follow-up angiography.

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H. Gordon Deen Jr., Richard S. Zimmerman, Scott K. Swanson, and Thayne R. Larson

✓ Lumbar spinal stenosis is a common problem in elderly patients. In its more advanced forms, it typically causes intractable leg pain, but many patients also manifest varying degrees of bladder dysfunction. The goal of lumbar decompressive laminectomy is relief of leg pain and paresthesias, yet some patients also achieve improvement in bladder function. This study prospectively investigated patients with lumbar spinal stenosis to determine whether laminectomy had any effect on urological function. Of the 20 patients in the study, 10 were men and 10 women (average age 70.9 years). All patients had severe lumbar stenosis affecting between two and four spinal segments, and all reported some degree of bladder dysfunction. Cystoscopy and urodynamic testing were completed preoperatively. A standard decompressive laminectomy was performed over the appropriate number of spinal segments. Urodynamic studies were repeated at 2 and 6 months postoperatively. At the 6-month follow-up review, bladder function was subjectively improved in 12 patients (60%) and unchanged in eight (40%). Postvoiding residual urine volume was the urodynamic factor most likely to be improved by laminectomy. In nine patients (45%), baseline postvoiding residual urine volume was elevated and all nine had improvement postoperatively. In the remaining 11 patients (55%), this urine volume was normal before and after surgery. Maximum urine flow rates also improved, but the results of cytometrography and electromyography, urine flow pattern, and bladder capacity were unchanged postoperatively. Cystoscopy detected previously undiagnosed malignancy of the lower urinary tract in two patients (10%). It is concluded that lumbar decompressive laminectomy can have a beneficial effect on bladder function in a significant number of patients with advanced lumbar spinal stenosis.

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H. Gordon Deen Jr, Richard S. Zimmerman, Mark K. Lyons, Malcolm C. McPhee, Joseph L. Verheijde, and Susan M. Lemens

✓ A prospective study of patients with neurogenic claudication and lumbar spinal stenosis was undertaken to determine whether measurement of exercise tolerance on the treadmill would be useful in defining baseline functional status and response to surgical treatment. Twenty patients with an average age of 73 years, all of whom had intractable neurogenic claudication and radiographically confirmed severe lumbar spinal stenosis, were studied. Lumbar decompressive laminectomy was performed in all patients. Preoperatively and 2 months postoperatively, quantitative assessment of ambulation was conducted on a treadmill at 0° ramp incline at two different speeds: 1.2 mph and the patient's preferred walking speed. The following information was recorded: time to first symptoms, time to severe symptoms, and nature of symptoms (leg pain, back pain, or generalized fatigue). The examination was stopped after 15 minutes or at the onset of severe symptoms.

In the preoperative 1.2-mph trial, the mean time to first symptoms was 2.68 minutes (median 1.31) and the mean time to severe symptoms was 5.47 minutes (median 3.42). In the postoperative trial at the same speed, 13 patients (65%) were able to walk symptom free for 15 minutes. The mean time to first symptoms was 11.12 minutes (median 15) and the mean time to severe symptoms was 11.81 minutes (median 15). Similar findings were recorded in the preferred walking—speed trials. There were no complications from the treadmill testing procedure. These findings indicate that exercise stress testing on a treadmill is a safe, easily administered, and quantifiable means of assessing baseline functional status and outcome following laminectomy in patients with symptomatic lumbar spinal stenosis.

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H. Gordon Deen, Richard S. Zimmerman, and Louis A. Lanza

✓ A method is described in which anterior fusion of the thoracic vertebral column is performed using a rib strut graft maintained on its vascular pedicle. This straightforward technique is useful in selected patients undergoing anterior thoracic fusion procedures and can be used in conjunction with other anterior spinal implants. By maintaining bone graft blood supply, this technique promotes an optimum fusion environment, which may enhance the speed of graft incorporation and the ultimate strength of the construct.

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Mark K. Lyons, John L. D. Atkinson, Robert E. Wharen, H. Gordon Deen, Richard S. Zimmerman, and Susan M. Lemens

Object. The authors report a retrospective analysis of 194 patients surgically treated at their institutions for symptomatic lumbar synovial cysts from January 1974 to January 1996.

Methods. Patient characteristics including age, sex, symptoms, signs, and preoperative neuroimaging studies were reviewed. Surgical procedures, complications, results, and pathological findings were correlated with preoperative assessment. One hundred ninety-four patients were surgically treated for symptomatic lumbar synovial cysts. Eighty percent were diagnosed and treated between 1987 and 1996. There were 100 men and 94 women with an average age of 66 years (range 28–94 years). The most common symptoms were painful radiculopathy (85%) and neurogenic single or multiroot claudication (44%). However, sensory loss (43%) and motor weakness (27%) were also presenting symptoms. Eleven percent of patients had undergone previous lumbar surgery prior to being referred to the Mayo Clinic. Preoperative neurological examination demonstrated motor weakness (40%), sensory loss (45%), reflex changes (57%), and variants of cauda equina syndrome (13%). In 19% of patients, normal neurological status was demonstrated. There was equal left/right-sided laterality, and eight patients presented with bilateral synovial cysts. The most commonly affected level was L4–5 (64%). All patients underwent laminectomy and resection of the cyst. Concomitant fusion was performed in 18 patients in whom clinical evidence of instability had been observed. However, subsequent fusion was required in only four patients who developed symptomatic spondylolisthesis. Surgery-related complications included cerebrospinal fluid leak (three patients), discitis (one patient), epidural hematoma (one patient), seroma (one patient), and deep vein thrombosis (one patient). One patient died 3 days after surgery of cardiac dysrhythmia. Follow-up data obtained for at least 6 months postoperatively were available in 147 patients. Of these, 134 (91%) reported good relief of their pain and 82% experienced improvement in their motor deficits.

Conclusions. Lumbar synovial cysts are a more common cause of lumbar radicular pain than previously thought. Surgical removal of the cyst is a safe and effective treatment for symptomatic relief in patients with lumbar synovial cysts. A concomitant fusion procedure may be performed in select cases. In this study, only a few patients developed symptomatic spinal instability requiring a second operation.

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Sanjeet S. Grewal, Richard S. Zimmerman, Gregory Worrell, Benjamin H. Brinkmann, William O. Tatum, Amy Z. Crepeau, David A. Woodrum, Krzysztof R. Gorny, Joel P. Felmlee, Robert E. Watson, Joseph M. Hoxworth, Vivek Gupta, Prasanna Vibhute, Max R. Trenerry, Timothy J. Kaufmann, W. Richard Marsh, Robert E. Wharen Jr., and Jamie J. Van Gompel


Although it is still early in its application, laser interstitial thermal therapy (LiTT) has increasingly been employed as a surgical option for patients with mesial temporal lobe epilepsy. This study aimed to describe mesial temporal lobe ablation volumes and seizure outcomes following LiTT across the Mayo Clinic’s 3 epilepsy surgery centers.


This was a multi-site, single-institution, retrospective review of seizure outcomes and ablation volumes following LiTT for medically intractable mesial temporal lobe epilepsy between October 2011 and October 2015. Pre-ablation and post-ablation follow-up volumes of the hippocampus were measured using FreeSurfer, and the volume of ablated tissue was also measured on intraoperative MRI using a supervised spline-based edge detection algorithm. To determine seizure outcomes, results were compared between those patients who were seizure free and those who continued to experience seizures.


There were 23 patients who underwent mesial temporal LiTT within the study period. Fifteen patients (65%) had left-sided procedures. The median follow-up was 34 months (range 12–70 months). The mean ablation volume was 6888 mm3. Median hippocampal ablation was 65%, with a median amygdala ablation of 43%. At last follow-up, 11 (48%) of these patients were seizure free. There was no correlation between ablation volume and seizure freedom (p = 0.69). There was also no correlation between percent ablation of the amygdala (p = 0.28) or hippocampus (p = 0.82) and seizure outcomes. Twelve patients underwent formal testing with computational visual fields. Visual field changes were seen in 67% of patients who underwent testing. Comparing the 5 patients with clinically noticeable visual field deficits to the rest of the cohort showed no significant difference in ablation volume between those patients with visual field deficits and those without (p = 0.94). There were 11 patients with follow-up neuropsychological testing. Within this group, verbal learning retention was 76% in the patients with left-sided procedures and 89% in those with right-sided procedures.


In this study, there was no significant correlation between the ablation volume after LiTT and seizure outcomes. Visual field deficits were common in formally tested patients, much as in patients treated with open temporal lobectomy. Further studies are required to determine the role of amygdalohippocampal ablation.