Reduced stroke risk in patients with compromised cerebral blood flow reactivity treated with superficial temporal artery to distal middle cerebral artery bypass surgery.

Extracranial-to-intracranial (EC-IC) bypass surgery for the prevention of stroke in patients with symptomatic carotid artery occlusion has nearly ended after a randomized trial showed no benefit of the procedure. Although an EC-IC bypass might benefit patients with compromised cerebrovascular hemodynamics, the randomized trial did not differentiate patients with hemodynamic from embolic etiologies. However, subsequent investigators have identified a subgroup of patients at increased stroke risk from hemodynamic compromise. Methods: We examined the subsequent stroke rate of 42 patients with symptomatic carotid occlusion at high risk for stroke identified as having a baseline cerebral blood flow (CBF)<45 mL/100 g/min and a >5% CBF reduction in one vascular territory after a vasodilatory challenge from 1 g of intravenous acetazolamide on stable xenon-computed tomography (CT) CBF imaging. Results: Thirty patients (group 1) treated medically were a subgroup with carotid occlusion from our long-term natural history study. During a median follow-up of 12 months, 9 patients (30%) had a new stroke within a median of 5 months. Twelve patients (group 2) had recurrent, disabling cerebral ischemic symptoms, with 8 progressing to mild fixed neurological deficits from deep white matter infarction identified on CT. All were treated with superficial temporal artery to distal middle cerebral artery (STA-MCA) bypass with restoration of cerebrovascular reserve postoperatively; none had a stroke during the 18-month minimum follow-up (P=.041). Perioperative morbidity included subendocardial infarction in one and a small, asymptomatic left frontal hemorrhage in another patient. Early postoperative and delayed xenon/CT CBF studies obtained a median of 5 months postoperatively showed maintenance of cerebrovascular reserve. Conclusion: STA-MCA bypass surgery can restore cerebrovascular reserve in high-risk patients with symptomatic internal carotid artery occlusion. This was achieved with minimal perioperative complications, resulting in a subsequent reduction of stroke frequency. We suggest that the efficacy of STA-MCA bypass surgery for symptomatic carotid occlusion be re-examined prospectively using hemodynamic selection criteria.     

Long-term assessment of cerebral perfusion following STA-MCA by-pass in patients

A prospective study of mean hemispheric cerebral blood flow (CBF) correlated with clinical status has now been completed for the past 54 months. Thirty-eight patients underwent superficial temporal to middle cerebral artery (STA-MCA) by-pass. They were compared with 22 patients with similar arteriographic lesions and clinical symptoms, treated medically throughout the same interval of time. Assignment to either treatment group was not randomized but depended solely on choice of patient or treating physician. Both groups were matched for age, clinical symptoms, angiographic abnormalities, and CBF values. All patients had proximal occlusion of one internal carotid artery or intracranial occlusive disease of the internal carotid or middle cerebral arteries. CBF measurements and clinical evaluations were repeated at regular intervals up to 54 months following surgery or institution of medical treatment. Mean follow up interval after STA-MCA by-pass was 28.7 months and for medical treatment was 29.7 months. Mean hemispheric CBF values for STA-MCA patients became significantly increased 2 weeks after operation. After that, CBF flow values decreased. At 24 months after surgery, flow values for surgically treated patients were significantly higher than among those treated medically, although there were no differences in flow values between the two groups at 3, 6, 12, 36 and 48 months. Prospective clinical evaluations after STA-MCA by-pass were as follows: 12 (32%) improved with cessation of TIAs and/or neurological improvement, 16 (42%) remained unchanged, 7 (18%) deteriorated (due to new or recurrent strokes) and 3 (8%) expired. Clinical results were the same for medical treatment: 6 (27%) improved, 10 (46%) unchanged, 4 (18%) deteriorated due to new or recurrent stroke, and 2 (9%) expired.     

Additional predisposing risk factors for atherothrombotic cerebrovascular disease among treated hypertensive volunteers

A 7-year prospective study of a cohort of 107 neurologically normal elderly hypertensive volunteers (mean age, 65.8 +/- 8.3 years) was undertaken to investigate the predictive validities of additional risk factors for atherothrombotic cerebrovascular disease including stroke, transient ischemic attacks, reversible ischemic neurological deficits, and multi-infarct dementia. This longitudinal study has been in progress now for 7 years with a mean follow-up interval of 50.12 +/- 5.76 months. Among 107 formerly symptom-free, normal hypertensive volunteers, 25 (23%) have developed cerebrovascular disease, 7 (6.5%) sustained a stroke, 10 (9.3%) developed multi-infarct dementia, and 18 (16.8%) have transient ischemic attacks. None have suffered intracranial hemorrhage. Mean gray matter cerebral blood flow (CBF) values measured at the initial visit were sensitive predictors of cerebrovascular disease. Eight of 16 hypertensives (50%) with initial CBF values below 60.0 ml/100 g/min now exhibit signs and symptoms of cerebrovascular disease, while 11 of 43 hypertensives (25.6%) with initial CBF values between 60.1 and 69.9 ml/100 g/min and only 6 of 48 (12.5%) with initial CBF levels above 70.0 developed cerebrovascular disease. Incidence of cerebrovascular disease among cigarette smoking hypertensive volunteers (32.5%) was significantly greater than among nonsmokers (17.2%).     

Prognosis of high-risk patients with nonoperated symptomatic extracranial carotid tight stenosis

Forty-five patients with symptomatic (20 with transient ischemic attack, 25 with minor stroke) greater than or equal to 75% stenosis of the cervical internal carotid artery had no endarterectomy and received only medical therapy because the surgical risks (severe cardiac disease, chronic obstructive pulmonary disease, hypertension or diabetes with systemic complications, aortic aneurysm) were believed to be unacceptable. During follow-up (mean 48 months), occlusion of the internal carotid artery developed without symptoms in two patients and with symptoms in three patients. The cumulative stroke and/or death rate was 24% at 2 years and 50% at 6 years. The ipsilateral infarct rate was 10% after the first year, but decreased markedly thereafter (2.4% per year), and one third of these infarcts were probably lacunes due to hypertensive small vessel disease. Overall, stroke related to previously symptomatic internal carotid artery stenosis was not the major problem during follow-up but was largely overcome by other strokes and cardiac death.     

The Effect of Valsartan versus Non-RAAS Treatment on Autoregulation of Cerebral Blood Flow

Background: Cerebral autoregulation (CA) is a protective mechanism which maintains the steadiness of the cerebral blood flow (CBF) through a broad range of systemic blood pressure (BP). Acute hypertension has been shown to reduce the cerebrovascular adaptation to BP variations. However, it is still unknown whether CA is impaired in chronic hypertension. This study evaluated whether a strict control of BP affects the CA in patients with chronic hypertension, and compared a valsartan-based regimen to a regimen not inhibiting the renin-angiotensin-aldosterone system (non-RAAS). Methods: Eighty untreated patients with isolated systolic hypertension were randomized to valsartan 320 mg or to a non-RAAS regimen during 6 months. The medication was upgraded to obtain BP <140/90 mm Hg. Continuous recordings of arterial BP and CBF velocity (transcranial Doppler) were performed during periods of 5 minutes, at rest, and at different levels of alveolar CO(2) pressure provided by respiratory maneuvers. The dominant frequency of CBF oscillations was determined for each patient. Dynamic CA was measured as the mean phase shift between BP and CBF by cross-spectral analysis in the medium frequency and in the dominant CBF frequency. Results: Mean ambulatory 24-hour BP fell from 144/87 to 127/79 mm Hg in the valsartan group and from 144/87 to 134/81 mm Hg in the non-RAAS group (p = 0.13). Both groups had a similar reduction in the central BP and in the carotido-femoral pulse wave velocity. The average phase shift between BP fluctuations and CBF response at rest was normal at randomization (1.82 ± 0.08 s), which is considered a preserved autoregulation and increased to 1.91 ± 0.12 s at the end of study (p = 0.45). The comparison of both treatments showed no significant difference (-0.01 ± 0.17 s vs. 0.16 ± 0.16 s, p = 0.45) for valsartan versus non-RAAS groups. The plasmatic level of glycosylated hemoglobin decreased in the valsartan arm compared to the non-RAAS arm (-0.23 ± 0.06 vs. -0.08 ± 0.07%, p = 0.07). Conclusions: In elderly hypertensive men with isolated chronic systolic hypertension, CA seems efficient at baseline and is not significantly affected by 6 months of BP-lowering treatment. This suggests that the preventive effects of BP medication against stroke are not mediated through a restoration of the CA.     

Neuropsychological assessments in relation to CBF after severe head injuries

OBJECTIVE: To determine whether neuropsychological outcome is related to cerebral blood flow (CBF) early in the recovery phase. MATERIAL AND METHODS: Twelve consecutive patients (mean age of 30 years, range 15-48 years) with severe traumatic brain injuries were subjected to a neuropsychological test battery at admission to the rehabilitation unit and after 3, 6 and 12 months. CBF measurements were performed at admission and 6 and 12 months later with a high-resolution, two-dimensional regional cerebral blood flow system with 254 stationary detectors after 1 min of (133)Xe inhalation (70-100 MBq/l). RESULTS AND CONCLUSION: Mean CBF values were within normal range already in the early post-acute phase and remained virtually unchanged during the first year of rehabilitation. A correlation was found between the individual CBF level and neuropsychological outcome 1 year after injury, particularly with regard to verbal memory capacity, reasoning capacity, and information processing speed.     

Autoregulation of cerebral blood flow in patients with orthostatic hypotension after spinal cord injury

Two groups of patients who developed orthostatic hypotension (OH) after spinal cord injury (SCI) were studied. In the first group all patients (4 females and 6 males) were asymptomatic, whereas in the second group (1 female and 9 males) all had clinical manifestations of hypotension. All but 3 patients were tetraplegic, and these patients were paraplegic above the T6 level. For this study blood pressure (BP), heart rate and cerebral blood flow (CBF) velocity were measured simultaneously on a tilt table at 0, 30, 60, and 80 degrees. Cerebral blood flow in the middle cerebral artery was measured bilaterally utilising the transcranial Doppler technique. In asymptomatic patients the mean baseline (0 degrees) BP (110 +/- 16/70 +/- 77 mm Hg systolic/diastolic) was not significantly different from the BP (106 +/- 16/68 +/- 11 mm Hg) of symptomatic patients. The mean maximal change in BP during tilting in the asymptomatic group (-23 +/- 10/10 +/- 7 mm Hg) was also not significantly different when compared to the symptomatic group (-29 +/- 13/11 +/- 6 mm Hg). CBF in the symptomatic group during the hypotensive reaction at 80 degrees was 32.5 +/- 5 cm/sec, while at the same body position in the asymptomatic group it was 40.9 +/- 8 cm/sec (significant at the p less than 0.02). In addition, CBF decreased in the symptomatic group at 80 degrees to 55.5 +/- 9.6% of baseline, while in the asymptomatic group the fall was 69.3 +/- 7.2% (p less than 0.001). Our data suggest that autoregulation of CBF rather than systemic BP plays a dominant role in the adaptation to OH in patients with SCI.     

Outcome of carotid artery occlusion is predicted by cerebrovascular reactivity

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the possibility of obtaining prognostic indications in patients with internal carotid occlusion on the basis of intracranial hemodynamic status, presence of previous symptoms of cerebrovascular failure, and baseline characteristics. METHODS: Cerebral hemodynamics were studied with transcranial Doppler ultrasonography. Cerebrovascular reactivity to apnea was calculated by means of the breath-holding index (BHI) in the middle cerebral arteries. Sixty-five patients with internal carotid artery occlusion were followed-up prospectively (median, 24 months), 23 patients were asymptomatic and 42 symptomatic (20 with transient ischemic attack and 22 with stroke). RESULTS: During the follow-up period, 11 symptomatic patients and 1 asymptomatic patient had another ischemic event ipsilateral to carotid occlusion. Among factors considered, only lower BHI values in the middle cerebral arteries ipsilateral to carotid occlusion and older age were significantly associated with the risk of developing symptoms (P=0.002 and P=0.003, respectively; Cox regression multivariate analysis). Based on our data, a cut point of the BHI value for distinguishing between pathological and normal cerebrovascular reactivity was determined to be 0.69. All patients except one, who developed TIA or stroke during the follow-up period, had BHI values ipsilateral to carotid occlusion of <0.69. CONCLUSIONS: These data suggest that impaired cerebrovascular reactivity is predictive for cerebral ischemic events in patients with carotid occlusion.     

Xenon-enhanced computed tomography cerebral blood flow measurements in acute cerebral ischemia: Review of 56 cases

Objective: Ischemic stroke must be diagnosed promptly if patients are to be treated with thrombolytic therapy. The diagnosis of acute cerebral ischemia, however, is usually based on clinical and computed tomography (CT) scan findings. CT scans are often normal in the first few hours after stroke. The purpose of this study was to determine whether Xenon-enhanced CT (XeCT) cerebral blood flow (CBF) studies could increase the sensitivity of stroke detection in the acute stage. Methods: CBF studies performed within 8 hours of symptom onset were evaluated in 56 patients who presented with hemispheric stroke symptoms. Mean CBF in the symptomatic vascular territory was calculated and compared with the corresponding contralateral area. CBF values below 18 mL/100g/min on 2 adjacent regions of interest were considered ischemic lesions. CT scans and angiograms were compared with the XeCt findings. Neurological condition on admission and discharge was evaluated by using National Institutes of Health Stroke Scale (NIHSS) scores. Results: The mean NIHSS score on admission was 12+/-5. Early CT scans were abnormal in 28 (50%) patients. There were 9 (16%) patients who had normal XeCT scans because of spontaneous reperfusion of the ischemic area. XeCT studies showed an ischemic lesion in 47 (84%) patients. In these patients, the mean CBF in the affected vascular territory was 16+/-8 mL/100g/min compared with 35+/-13 mL/100g/min in the contralateral specular territory (P<0.001). There were no false positive or negative XeCT studies, and the location of the perfusion defect corresponded with the CT and/or angiographic findings in all cases. Eight patients died (14%), and the 48 survivors (86%) had a mean NIHSS score of 9+/-6 on discharge. Conclusions: CBF measurements were correlated with the CT and angiographic results and greatly assisted in the diagnosis of acute ischemic stroke. XeCT studies used for estimating the location and extent of cerebral ischemia may be important in the triage of patients for acute stroke therapy.     

Decreased cerebral blood flow precedes multi-infarct dementia, but follows senile dementia of Alzheimer type

A 7-year prospective study among 181 neurologically normal elderly volunteers (mean age, 70.6 years) revealed an incidence of 3.3%, or 0.47% new cases per year, for Alzheimer's disease (SDAT) and 5.5%, or 0.78% new cases per year, for multi-infarct dementia (MID). The unusually high incidence of MID is considered to reflect preselection of a large percentage of volunteers (48.6%) with risk factors for (but without symptoms of) atherothrombotic stroke. Of 88 volunteers at risk of stroke, 11.4% developed MID within 7 years. In MID patients, cerebral blood flow (CBF) values began to decline around 2 years before onset of symptoms, while in SDAT patients, CBF levels remained normal until symptoms of dementia appeared; thereafter, CBF declined rapidly.     

A Pilot Study of Microembolic Signals in Patients With Middle Cerebral Artery Stenosis

OBJECTIVE: There has been limited data on the frequency of microembolic signals in patients with middle cerebral artery (MCA) stenosis, especially during the acute phase of stroke. Using transcranial Doppler, the authors prospectively monitored the MCA segments distal to stenosis in 4 groups of patients for 30 minutes: (1) symptomatic patients with acute ischemic stroke and MCA stenosis, (2) asymptomatic group patients with asymptomatic MCA stenosis, (3) control patients with acute ischemic stroke of undetermined etiology, and (4) normal people. A total of 60 patients completed the study. There were no microembolic signals in the asymptomatic, control, and normal groups. Among 20 patients in the symptomatic group, microembolic signals were detected in 3 patients (15%). The number of emboli ranged from 1 to 6 per 30 minutes. This is the first report of the presence of microembolic signals in acute stroke patients with MCA stenosis.     

Progressive cerebral ischemia antedates cerebrovascular symptoms by two years

Prospective longitudinal cerebral blood flow values were serially plotted over a four-year interval against the course of cerebral ischemia before, during, and after onset of clinical symptoms. Of 161 normal subjects (mean age, 62 years), 86 were risk free and 75 had hypertension, heart disease, diabetes mellitus, and/or hyperlipidemia. Twenty-one subjects developed cerebrovascular symptoms during the prospective trial. Mean hemispheric cerebral blood flow values were significantly lower for at risk than for risk-free subjects. Symptomatic subjects showed lower values than those in either of the two asymptomatic groups at every session. Statistical analysis of cerebral blood flow values for symptomatic patients compared one and two years prior to onset of symptoms, at the onset of symptoms, and 1 year later showed reductions compared to asymptomatic risk-factored subjects tested in a similar prospective manner. Measurable declines in cerebral perfusion accompany development and progression of aortocerebral atherosclerosis prior to clinical appearance of signs and symptoms of cerebrovascular disease. If confirmed, these observations should permit the institution of preventive medical and/or surgical interventive measures and an evaluation of their outcome.     

How good is the management of vascular risk after stroke, transient ischaemic attack or carotid endarterectomy?

BACKGROUND: Patients remain at high risk of vascular events after stroke, transient ischaemic attack or carotid endarterectomy. We studied how well this risk is addressed by the effective treatment of modifiable risk factors. METHODS: A total of 198 consecutive attenders at a rapid access stroke clinic and 98 consecutive patients undergoing carotid endarterectomy were studied. Treatment of hypertension and hyperlipidaemia, smoking status and the use of antithrombotic therapy were assessed at baseline and 6 months later. The findings were compared with targets from the UK National Clinical Guidelines for Stroke. RESULTS: Baseline and follow-up data were available on 284 patients. The rates of control of vascular risk factors improved only slightly during follow-up. Blood pressure was below target levels in only 69 (24%) at baseline and 79 (28%) at 6 months, and serum cholesterol was below target levels in only 55 (19%) at baseline and 63 (22%) at 6 months. At baseline, 55 (19%) were smokers, of whom 12 (22%) had quit at 6 months. Anticoagulant therapy was prescribed in 19 of 37 patients (51%) in atrial fibrillation at 6 months. Antiplatelet therapy was prescribed in 90% of patients in sinus rhythm. CONCLUSIONS: Despite the identification of vascular risk factors at the time of clinic or surgery, 6 months later these risk factors remain poorly addressed. More effective methods of managing vascular risk in these patients are needed.     

Recovery from cerebral ischaemia. EEG, cerebral blood flow and clinical symptomatology in the first three years after a stroke

In 43 patients suffering from unilateral supratentorial ischaemia the changes over an interval of 3 years in clinical score, quantified EEG (using the neurometric method) and CBF (Xenon inhalation method) were studied. The patients were examined 3 times: shortly after the onset of ischaemia and respectively 3 and 36 months after this first measurement. Three patients died from causes not related to cerebral ischaemia. In the surviving patients the EEG and clinical score improved, often dramatically; the CBF values did not change significantly. Most of the changes occurred in the first 3 months after the stroke. For the evaluation of the prognostic value of the various parameters, 2 sub-groups of patients with different outcome but comparable initial clinical scores were studied. A persistent neurological deficit was predicted by a low CBF at the first measurement. The neurometric parameters obtained from the initial EEG had no value in this respect.     

Relationship between cerebral blood flow and clinical outcome in acute stroke

OBJECTIVE: The purpose of this study was to determine the relationship between cerebral blood flow (CBF) measurements in acute stroke and early clinical outcome. MATERIAL AND METHODS: The xenon-enhanced computed tomography (XeCT) CBF studies performed in 50 patients in the acute stage (within 8 h) of a hemispheric stroke were retrospectively analyzed. The mean CBF of the symptomatic vascular territory was compared to the corresponding territory in the contralateral hemisphere. Clinical assessment on admission and discharge was performed using the National Institutes of Health stroke scale (NIHSS). RESULTS: Three groups were defined according to the degree of CBF asymmetry between the symptomatic and the contralateral asymptomatic vascular region. The CBF asymmetry was mild in group A (< or =20%), moderate in group B (>20% and <60%) and severe in group C (> or =60%). Patients in group A (n = 18) had a good outcome with a mean NIHSS score of 2 +/- 2 at discharge. In group B, the patients (n = 22) had intermediate but variable outcomes: 2 patients died and the mean NIHSS score for the survivors was variable (mean NIHSS score: 9 +/- 6). The patients in group C (n = 10) had a very poor outcome: 4 patients died and the survivors had a mean NIHSS score of 15 +/- 1. CONCLUSIONS: Quantitative XeCT CBF measurements may be useful for selecting subgroups of stroke patients with different clinical outcomes. The possibility of predicting patient prognosis as early as in the first hours after the ischemic event may help to identify the appropriate target population that will benefit from aggressive stroke therapy.     

Nonfasting serum glucose and insulin concentrations and the risk of stroke.

BACKGROUND AND PURPOSE: Type 2 diabetes is an established risk factor for stroke, but the relations between asymptomatic hyperglycemia, hyperinsulinemia, and stroke incidence remain uncertain. We have examined the relationship between established diabetes, nonfasting serum glucose and serum insulin concentrations, and subsequent risk of stroke. METHODS: We performed a prospective study of 7735 men aged 40 to 59 years drawn from general practices in 24 British towns. Men with missing serum glucose values (n=50) and men on insulin injection (n=36) were excluded, leaving 7649 men available for analysis. Baseline nonfasting serum was analyzed for insulin with a specific enzyme-linked immunosorbent assay method in 18 of the 24 towns (n=5663 men). RESULTS: During the mean follow-up period of 16.8 years, there were 347 stroke cases (fatal and nonfatal) in the 7649 men. Men who developed diabetes during follow-up (n=320) and men with established type 2 diabetes at screening (n=98) both showed significantly increased risk of stroke, even after adjustment for cardiovascular risk factors, including blood pressure (adjusted relative risk [RR], 2.27; 95% CI, 1.23 to 4.20; RR, 2.07; 95% CI, 1. 44 to 2.98, respectively). In men with no diagnosed diabetes at screening (n=7551), risk of stroke was increased significantly only in the top 2.5% of the nonfasting glucose distribution (>/=8.2 mmol/L), and this persisted even after adjustment for cardiovascular risk factors, including hypertension (RR, 1.86; 95% CI, 1.11 to 3. 13). Exclusion of the 320 men who developed diabetes during follow-up attenuated this risk so that it was no longer significant (RR, 1.56; 95% CI, 0.83 to 2.91). In the 5567 men with insulin measurements and no diagnosis of diabetes at screening, a J-shaped relationship was seen between nonfasting insulin and risk of stroke. Risk was significantly raised in the first quintile and in the fourth quintile and above compared with the second quintile, with all findings of marginal significance. Part of the increased risk at higher levels of insulin was due to men who developed diabetes in the follow-up period. CONCLUSIONS: This study confirms the importance of established type 2 diabetes as an independent risk factor for stroke. The increased risk of stroke seen in hyperglycemic subjects and those with elevated serum insulin levels at screening reflected to some extent the high proportion of men who subsequently developed diabetes.     

Embolism in acute middle cerebral artery stenosis

OBJECTIVE: To investigate the frequency of middle cerebral artery (MCA) stenosis in a series of nonselected patients and the coexistence of microembolic signals with stenosis. METHODS: MCA stenosis was sought by transcranial Doppler (TCD) in 387 patients admitted consecutively with acute ischemic cerebrovascular disease within the first 48 hours of the onset of symptoms and again at 6 months. TCD monitoring for microembolic signals was performed on all patients with MCA stenosis. RESULTS: MCA stenoses were found in 29 patients (7%), although in only 20 patients (5%) was the stenosis symptomatic. Microembolic signals were detected in five of 14 symptomatic stenoses (36%) monitored at the acute phase, but none were found in the chronic phase or in asymptomatic stenosis. Despite one third of symptomatic patients having had a further source of emboli, microembolic signals were detected only distally to the MCA stenosis. In the symptomatic group, 25% of stenoses had completely disappeared 6 months after stroke. Microembolic signal detection at the acute phase was associated with the subsequent disappearance of the stenosis. CONCLUSIONS: The frequency of symptomatic MCA stenosis in acute ischemic stroke was 5% in the population studied. Many stenoses are transient, and microembolic signals are often detectable at the poststenotic segment in the acute phase. The origin of at least 25% of symptomatic acute MCA stenoses may be embolic rather than atherosclerotic.     

Cerebral blood flow and cognitive testing correlate in Huntington's disease

Brain atrophy estimated by computed tomographic (CT) scanning and mean hemispheric and regional gray matter cerebral blood flow (CBF) values were measured in patients with mild to moderate Huntington's disease (HD) (N = 16) using the xenon Xe 133 inhalation method and in asymptomatic blood relatives at risk from HD (N = 6) using both the xenon Xe 133 inhalation and the stable xenon CT contrast CBF methods. Results were compared with measurements in two groups of age-matched normal volunteers (N = 48 and N = 42, respectively). Significant brain atrophy in the vicinity of both caudate nuclei was present in patients with HD but not in at-risk individuals. Mean hemispheric xenon Xe 133 CBF values were reduced in patients with HD but seemed to be normal in at-risk individuals. In HD, reductions in CBF were found in both frontotemporal regions. Correlations were found between severity of dementia estimated by reductions of Mini-Mental Status Questionnaire scores and reductions of either mean hemispheric or regional frontotemporal CBF values in HD. The CT estimates of brain atrophy and three-dimensional CBF by stable xenon-contrast measurements were normal in asymptomatic individuals at risk from HD.     

Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia

Progressive brain damage after transient cerebral ischemia may be related to changes in postischemic cerebral blood flow and metabolism. Regional cerebral blood flow (rCBF) and cerebral glucose utilization (rCGU) were measured in adult rats prior to, during (only rCBF), and serially after transient forebrain ischemia. Animals were subjected to 30 minutes of forebrain ischemia by occluding both common carotid arteries 24 hours after cauterizing the vertebral arteries. Regional CBF was measured by the indicator-fractionation technique using 4-iodo-[¹⁴C]-antipyrine. Regional CGU was measured by the 2-[¹⁴C]deoxyglucose method. The results were correlated with the distribution and progression of ischemic neuronal damage in animals subjected to an identical ischemic insult. Cerebral blood flow to forebrain after 30 minutes of moderate to severe ischemia ( < 10% control CBF) was characterized by 5 to 15 minutes of hyperemia; rCBF then fell below normal and remained low for as long as 24 hours. Postischemic glucose utilization in the forebrain, except in the hippocampus, was depressed below control values at 1 hour and either remained low (neocortex, striatum) or gradually rose to normal (white matter) by 48 hours. In the hippocampus, glucose utilization equaled the control value at 1 hour and fell below control between 24 and 48 hours. The appearance of moderate to severe morphological damage in striatum and hippocampus coincided with a late rise of rCBF above normal and with a fall of rCGU; the late depression of rCGU was usually preceded by a period during which metabolism was increased relative to adjacent tissue. Further refinement of these studies may help identify salvageable brain after ischemia and define ways to manipulate CBF and metabolism in the treatment of stroke.     

Significance of a reduced cerebral blood flow during the first 12 hours after traumatic brain injury

Background: It is controversial whether a low cerebral blood flow (CBF) simply reflects the severity of injury or whether ischemia contributes to the brain’s injury. It is also not clear whether posttraumatic cerebral hypoperfusion results from intracranial hypertension or from pathologic changes of the cerebral vasculature. The answers to these questions have important implications for whether and how to treat a low CBF. Methods: We performed a retrospective analysis of 77 patients with severe traumatic brain injury who had measurement of CBF within 12 hours of injury. CBF was measured using xenon-enhanced computed tomography (XeCT). Global CBF, physiological parameters at the time of XeCT, and outcome measures were analyzed. Results: Average global CBF for the 77 patients was 36±16 mL/100g/minutes. Nine patients had an average global CBF <18 (average 12±5). The remaining 68 patients had a global CBF of 39±15. The initial ICP was >20 mmHg in 90% and >30 mmHg in 80% of patients in the group with CBF<18, compared to 33% and 16%, respectively, in the patients with CBF≥18. Mortality was 90% at 6 months postinjury in patients with CBF<18. Mortality in the patients with CBF>18 was 19% at 6 months after injury. Conclusion: In patients with CBF<18 mL/100 g/minutes, intracranial hypertension plays a major causative role in the reduction in CBF. Treatment would most likely be directed at controlling intracranial pressure, but the early, severe intracranial hypertension also probably indicates a severe brain injury. For levels of CBF between 18 and 40 mL/100 g/minutes, the presence of regional hypoperfusion was a more important factor in reducing the average CBF.