Cerebellar Blood Flow Research Articles

Performance on neuropsychological tests related to single photon emission computerised tomography findings in frontotemporal dementia.

This study examines relations between regional cerebral blood flow (rCBF) and neuropsychological test results, age at onset and duration of disease in patients with frontotemporal-type dementia (FTD). Sixteen patients with a diagnosis of probable FTD were examined using single photon emission computerised tomography (SPECT) with 99mTc-HMPAO as the tracer. The rCBF of 14 regions of interest relative to cerebellar blood flow was calculated. Psychological tests assessing language, verbal fluency, memory and visuospatial constructive ability were given. Correlations were demonstrated between a global impairment score and relative blood flow in lateral frontal, medial frontal and left orbital frontal areas. Verbal fluency scores correlated with left lateral frontal, medial frontal and left anterior inferior temporal blood flow. No relationships between decrease in CBF and age at onset or duration of disease, or between impaired cognitive function and age at onset or duration of disease were found. The present study demonstrates a close coupling between reduced rCBF and specific neuropsychological deficits in FTD.

Alteration of rCBF in skull base lesions.

Cerebral functional imaging methods provide complementary information on brain function and large vessels regulatory controls which are compromised in cranial base lesions. The presence of a skull base tumor can alter regional cerebral blood flow (rCBF) in adjacent and remote brain tissue. This report presents the results of 104 CBF studies in 66 patients with skull base lesions (aged 17-75 years). The lesions included 36 meningiomas, 21 neurinomas and 9 other tumors. Regional CBF in tumor and brain tissue was measured prior to treatment using stable xenon enhanced computed tomography (Xenon(/T). For the quantitative analysis, regions of interest were delineated on tumor regions, cerebral and cerebellar hemispheres including peritumoral regions. In order to assess the remote effect of cerebellopontine angle (CPA) tumors, the brainstem, cerebellar, and cerebral blood flow were measured in 26 cases. The average brainstem CBF for patients with good outcome was higher than the average brainstem CBF for patients with poor outcome. This indicates that CBF studies in posterior fossa can be useful in predicting the prognosis of CPA tumor patients. We report a series of 16 patients with cavernous sinus tumors in whom the internal carotid artery was affected by the tumor. In nearly all cases Xenon/CT CBF studies with acetazolamide test showed no significant difference in hemispheric perfusion and a sufficient cerebrovascular reserve capacity. Interhemispheric asymmetry was present only in one patient. These results possibly indicate that i.v. administration of acetazolamide might contribute in selecting patients with higher risk for ischemic deficits after cavernous sinus surgery. Skull base meningiomas showed very high blood flow with a wide range. Local CBF in the peripheral region of meningiomas was higher than in the central region. Blood flow values in the peritumoral areas are about 30% lower than those of the ipsilateral hemisphere. In individual cases, blood flow values in the peritumoral low-density area on CT were extremely low. It is concluded that CBF studies in skull base tumors are valuable in treatment planning. Xenon/CT can be useful additional diagnostic procedure in the evaluation of skull base surgery candidates.

The effect of ethanol on alcohol‐responsive essential tremor: A positron emission tomography study

We used H2 15O positron emission tomography (PET) to investigate the effect of ethyl alcohol on regional cerebral blood flow in 6 patients with alcohol-responsive essential tremor and 6 age-matched control subjects. The patients were scanned while at rest and during involuntary postural tremor of the extended right arm. Normal control subjects were scanned at rest and during passive wrist oscillation of the right arm at tremor frequency. Regional cerebral blood flow associated with these conditions was measured before and after oral administration of 2 to 3 units of alcohol. The mean blood alcohol level was 35.3 +/- 20.0 mg/dl in the patient group and caused marked suppression of tremor; it was 33.9 +/- 12.9 mg/dl in the control group. Similar to previous PET studies on essential tremor patients, tremor compared with rest was associated with bilateral cerebellar activation including the cerebellar vermis. This pattern of activation differed from passive wrist oscillation where ipsilateral cerebellar activation was observed. Ethanol ingestion led to bilateral decreases of cerebellar blood flow in both tremor patients and normal subjects, and this was associated with suppression of tremor in the patients. Alcohol-associated increases of regional cerebral blood flow were observed in the inferior olivary nuclei in the patients but not in the control subjects. We conclude that alcohol-induced suppression of essential tremor is mediated via a reduction of cerebellar synaptic overactivity resulting in increased afferent input to the inferior olivary nuclei.

7-Nitroindazole attenuates vasodilation from cerebellar parallel fiber stimulation but not acetylcholine.

We used the relatively selective inhibitor of neuronal nitric oxide synthase 7-nitroindazole (7-NI) to test the hypothesis that the increases in local cerebellar blood flow (BFcrb) elicited by activation of the cerebellar parallel fibers (PF) are mediated by neuronal production of nitric oxide. In halothane-anesthetized rats, the cerebellar cortex was exposed and superfused with Ringer solution (37 degrees C; pH 7.3-7.4). The PF were stimulated electrically (100 microA, 30 Hz, 40 s), while BFcrb was monitored at the site of stimulation by a laser-Doppler flow probe. In vehicle-treated rats (n = 5), PF stimulation increased BFcrb by 61 +/- 5% (P < 0.05; analysis of variance and Tukey's test). 7-NI attenuated the increase in BFcrb dose dependently (10-100 mg/kg i.p.; n = 5 animals/dose) and by 55 +/- 7% at 100 mg/kg (P < 0.05). The attenuation of the response to PF stimulation was correlated with the degree of inhibition of calcium-dependent brain nitric oxide synthase activity, measured ex vivo by the citrulline assay (n = 21). 7-NI also attenuated the cerebrovasodilation elicited by hypercapnia (PCO2 = 50-60 mmHg) but did not affect the vasodilation evoked by acetylcholine (10 microM; n = 4; P > 0.05; t-test), a response mediated by endothelial nitric oxide synthase. 7-NI did not attenuate the BFcrb increase evoked by the nitric oxide donor S-nitroso-N-acetylpenicillamine (1 mM; n = 5; P > 0.05; t-test). Similarly, 7-NI did not affect resting systemic arterial pressure. These observations suggest that selective inhibition of neuronal nitric oxide synthase by 7-NI attenuates the increases in BFcrb evoked by PF stimulation. The findings provide additional support to the hypothesis that the increase in BFcrb evoked by PF stimulation is mediated, in part, by glutamate-induced activation of neuronal nitric oxide synthase.

Cerebellar and subcortical blood flow abnormalities in children with partial epilepsy

Cerebellar and cerebral subcortical blood flow in 41 children with partial epilepsy and 6 normal controls was investigated during the interictal state using single photon emission computed tomography with technetium-99m hexamethylpropyleneamineoxime. Seventeen of 41 patients had been treated with antiepileptic drugs (AEDs) for 4.65 ± 3.80 years (range 0.2–12) and 24 patients were drug-free. Unilateral hypoperfusion of cerebellum and cerebral subcortical gray matter was demonstrated in 11 (28%) and 16 (40%) patients, respectively. Most of them also had focal cerebral cortical perfusion abnormalities, ipsilateral or contralateral to the cerebellar and cerebral subcortical hypoperfusion. The mean asymmetry indices of cerebellar blood flow in the medicated and the unmedicated patients were significantly higher than in the control cases ( P ⩽ 0.02 and P ⩽ 0.04), whereas the differences in the asymmetry indices in cerebral subcortical areas were insignificant. AED therapy did not affect the perfusion of cerebellum and cerebral subcortical regions ( P > 0.05 and P > 0.05). Our results suggest that functional alterations on anatomically connected remote areas in patients with partial epilepsy are not related to the drug effect and probably due to primary epileptogenic activity.

A positron emission tomography study of primary orthostatic tremor

Primary orthostatic tremor (OT), a clinical syndrome in which a rapid (14 to 16 Hz), regular lower limb tremor causes unsteadiness on standing, may be associated with a postural upper limb tremor of similar frequency. We used H2 15O PET to analyze the abnormal pattern of cerebral activation associated with the postural upper limb tremor in four patients with primary OT. Patients had regional cerebral bloodflow (rCBF) measured during involuntary tremor while maintaining a posture with their outstretched right upper limb and again at rest. Tremor was associated with abnormal bilateral cerebellar and contralateral lentiform and thalamic activation. These findings were evident on group analysis of pooled PET data after transformation into standard stereotactic space and in single subjects when PET images were coregistered with structural MRI of the brain. At rest, cerebellar blood flow was significantly increased bilaterally in OT when compared with age- and sex-matched controls. We have previously demonstrated similar abnormal bilateral cerebellar activation in essential and writing tremors and conclude that abnormal bilateral overactivity of cerebellar connections is a common feature of tremulous disorders.

Neural mechanisms of blood flow regulation during synaptic activity in cerebellar cortex.

1. We investigated the neural mechanisms of the increases in blood flow produced by synaptic activity using the parallel fiber (PF) system of the cerebellum as a model. The midline cerebellum was exposed in anesthetized rats and the PFs were stimulated with tungsten microelectrodes. Cerebellar blood flow (BFcrb) was recorded using a laser-Doppler probe, whereas field potentials were recorded using glass micropipettes. PF stimulation produced increases in BFcrb that were related to the frequency and intensity of stimulation (+60 +/- 9%, mean +/- SE, at 100 microA and 30 Hz; n = 6). The greatest increases were confined to a band stretching along the major axis of the stimulated folium and corresponding to the beam of activated PFs. The increase in evoked by PF stimulation was associated with a corresponding increase in glucose utilization, assessed by the 2-deoxyglucose method. The increases in BFcrb and the field potentials evoked by PF stimulation were abolished by tetrodotoxin (1 microM; n = 6). Ringer solution containing 12 mM Mg2+ and 0 mM Ca2+ blocked synaptic activity in the PFs and abolished the increases in flow (P > 0.05 from baseline; n = 5). The broad-spectrum glutamate receptor antagonist kynurenate (5 mM) prevented depolarization of Purkinje cells and interneurons and abolished the increase in BFcrb evoked by PF stimulation (P > 0.05; n = 6). Treatment with tetrodotoxin, Mg2+, or kynurenate did not affect the increase in BFcrb elicited by systemic hypercapnia or by topical application of the nitric oxide donor 3-morpholino sydnonimine (P > 0.05 from Ringer solution). We conclude that the increases in flow produced by synaptic activity are linked to glutamate-induced depolarization of Purkinje cells and interneurons. These findings provide evidence that activation of glutamate receptors participates in the mechanisms of functional hyperemia, and they support the validity of the PF system as a model for study of the relationship between synaptic activity and blood flow in the CNS.

Changes in the Cerebral and Cerebellar Blood Flow in Cerebral Embolism

The present study was performed to elucidate the time course of the cerebral and cerebellar blood flows and the significance of SPECT for predicting the outcome in cerebral embolism. ^99mTc-hexamethylpropyleneamine oxime (^99mTc-HMPAO) SPECT was repeatedly performed in 60 patients with unilateral cerebral embolism. The distribution of ^99mTc-HMPAO in the infarct area decreased in the acute phase, increased from 3 h to 22 days after the stroke and then gradually and eventually decreased in the chronic stage. This tendency was observed irrespective of the thrombolytic therapy. The asymmetry index (AI) in the cerebral hemisphere in the first 6 h and later than 30 days correlated significantly with activities of daily living in the chronic stage (p &#60; 0.05). The cerebellar AI after, but not up to 14 days also correlated with the long-term outcome (p &#60; 0.05). In conclusion, a high distribution of ^99mTc-HMPAO frequently and transiently occurs in the subacute stage of cerebral embolism. The cerebral and cerebellar asymmetry of the ^99mTc-HMPAO distribution is an important predictive value for the outcome; however, the timing of SPECT is critically important.

The relation between crossed cerebellar blood flow and severities of hemiplegia: a technetium-(99m) hexamethylpropylene amine oxine SPECT study using Patlak plot method.

Crossed cerebellar diaschisis (CCD), decrease in crossed cerebellar blood flow (CCBF) (ml/100g/min), is often observed in the cerebral blood flow imaging of hemiplegic patients. We studied the relations between severities of hemiplegia and degrees of CCD. Severities of hemiplegia were evaluated by Brunnstrom stages (Br. stage) of lower limbs. Degree of CCD was evaluated as CCBF and asymmetry index (ASI) (%) of CCBF, which were calculated from technetium-(99m) hexamethylpropylene amine oxine ((99m)Tc HMPAO) SPECT study using Patlak plot method (Matsuda et al. 1992, 1993). We have studied twenty consecutive patients. The CCBF was significantly different between Br. stage II and IV (p = 0.0357), III and IV (p < 0.001) and III and V (p < 0.001). ASI was significantly different between II and IV (p = 0.0357), III and IV (p < 0.001) and III and VI (p = 0.0238). Both of CCBF and ASI of the group of II and III were significantly lower than those of the group of IV, V and VI (p = 0.0033 for CCBF and p = 0.0087 for ASI). We conclude that this study indicate a close correlation between the sevreties of hemplegia and the degrees of CCD.

SPECT abnormalities in generalized dystonia

A patient with severe, generalized dystonia and 6 age range-matched controls were studied with the regional cerebral blood flow tracer technetium-99m hexamethylpropyleneamine oxime by single-photon emission computed tomography to test the hypothesis that cerebellar function is abnormal in dystonia. Analysis was performed by drawing regions of interest around the caudate head nuclei, hemithalami, deep cerebellar nuclei, and cerebellar hemicortices. The counts in each region of interest were normalized to whole brain cerebral blood flow in an identical manner for each subject. The dystonic patient had a difference in regional cerebral blood flow between the right and left deep cerebellar nuclei, increased regional cerebral blood flow in subcortical motor structures, and an abnormal relationship between right cerebellar cortical and right deep cerebellar nuclear regional cerebral blood flow. The findings in this patient provide evidence that the cerebellum may play a role in the pathophysiology of motor signs in some patients with dystonia.

Cerebellar blood flow in schizophrenic patients and normal control subjects

We used 133Xe dynamic single-photon emission computed tomography (DSPECT) to measure the resting cerebellar blood flow in 17 neuroleptic-free schizophrenic and schizophreniform patients and 13 normal control subjects. A subset of these subjects (11 patients and 7 control subjects) additionally underwent activation studies during the Wisconsin Card Sorting (WCS) and Number Matching (NM) tests. Baseline relative cerebellar blood flow was significantly lower in older patients than in age-matched control subjects. For absolute cerebellar flow, there was a significant difference between patients and control subjects in the overall activation response (patients: 21.3% increase, control subjects: 6.5% increase) and WCS (patients: 16.5% increase, control subjects: 9.7% increase). The difference in the magnitude of cerebral NM activation between schizophrenic patients and control subjects, although not statistically significant, may call into question the appropriateness of using NM as a control task in schizophrenic patients. Finally, we found no differences between the effects of WCS and NM on cerebrelar or cerebral blood flow. Because of the small number of subjects in each group, the results of this study should be interpreted cautiously.

Nitric oxide contributes to functional hyperemia in cerebellar cortex

We used the parallel fibers (PF) system of the cerebellar cortex as a model to investigate the role of nitric oxide (NO) in the increases in blood flow elicited by neural activation. Rats were anesthetized with halothane and ventilated. The vermis was exposed, and the site was superfused with Ringer (37 degrees C; pH 7.3-7.4). PF were stimulated electrically (100 muA; 30 Hz), and the associated changes in cerebellar cortex blood flow (BFcrb) were monitored by laser-Doppler flowmetry. The field potentials evoked by PF stimulation were recorded using microelectrodes. During Ringer superfusion (n = 7), PF stimulation increased BFcrb (+ 52 +/- 4%). Topical application of the NO synthase (NOS) inhibitor N omega-nitro-L-arginine (L-NNA; 0.1-1 mM) attenuated the increases in BFcrb dose dependently and by 50 +/- 4% at 1 mM (n = 9; P < 0.001; analysis of variance and Tukey's test). L-NNA (1 mM) inhibited NOS catalytic activity, assessed ex vivo using the citrulline assay, by 95 +/- 9% (P < 0.001). L-NNA did not influence the field potentials evoked by PF stimulation. D-NNA (1 mM; n = 6), the inactive stereoisomer of nitroarginine, did not attenuate the BFcrb response (P > 0.05). Methylene blue (1 mM; n = 7) reduced the response by 41 +/- 9% (P < 0.01) without affecting NOS catalytic activity (P < 0.05). The increases in BFcrb were not affected by lesioning the NOS-containing nerve fibers innervating cerebral vessels, indicating that these nerves are not the source of NO. Thus the increases in BFcrb elicited by activation of PF are, in part, mediated by NO produced in the molecular layer during neural activity. The results indicated that NO participates in the coupling of function activity to blood flow and support the hypothesis that NO is one of the mediators responsible for functional hyperemia in the central nervous system.

Contralateral cerebellar diaschisis 7 hours after MCA-occlusion in primates

2,3,5-triphenyltetrazoliumchloride (TTC) as an indicator of mitochondrial function in combination with regional cerebral blood flow measurements was used in six baboons 6.9 +/- 1.2 h after permanent occlusion of the left middle cerebral artery. Staining with TTC was compared with blood flow data obtained during normocapnia using the microsphere method. Five animals showed a focal area of unstained tissue in the left middle cerebral artery territory. Mean blood flow in the unstained area was 28.3 +/- 15.4 ml min-1 100 g-1. Five of 6 animals showed a significant decrease of contralateral cerebellar blood flow in the presence of normal TTC staining. We conclude that at this early stage of infarction contralateral cerebellar diaschisis is caused by functional deactivation.

Crossed Cerebellar Diaschisis and Brain Recovery After Stroke

Although crossed cerebellar diaschisis is well recognized after stroke, there is controversy concerning its clinical correlations and serial changes, and little is known about its prognostic value. We studied crossed cerebellar diaschisis and cerebral hypoperfusion in 47 patients with acute middle cerebral cortical infarction using 99mTc-hexamethylpropyleneamine oxime and single-photon emission computed tomography within 72 hours of stroke onset. Thirty-one of these patients had outcome studies at 3 months; 15 of the 31 underwent an additional scan after acetazolamide injection. Tissue loss was determined with computed tomography, performed at outcome in 28 patients. Clinical stroke severity was assessed with the Canadian Neurological Scale and Barthel Index. Cerebellar blood flow asymmetry was studied in 22 healthy, age-matched control subjects. Cerebellar blood flow asymmetry was significant in patients (mean +/- SE, 9.76 +/- 0.78%; P < .001) but not in control subjects (-0.22 +/- 0.56%). Crossed cerebellar diaschisis was strongly associated with infarct hypoperfusion volume at both acute (regression coefficient +/- SEb, b = 6.76 +/- 0.65; P < .001) and outcome stages (b = 6.13 +/- 0.63; P < .001). Cross-sectionally over the first 72 hours, infarct hypoperfusion volume decreased by 2% for each hour from onset (P < .05), while crossed cerebellar diaschisis remained unchanged. Canadian Neurological Scale score at the acute stage was negatively associated with acute crossed cerebellar diaschisis (b = -0.10 +/- 0.05; P < .05) after allowing for infarct hypoperfusion volume. Crossed cerebellar diaschisis did not change between acute-stage, outcome, and postacetazolamide scans. Acute-stage crossed cerebellar diaschisis predicted outcome Barthel Index score (b = -0.28 +/- 0.14; P = .05) and tissue loss (b = 3.81 +/- 0.96; P < .001) but was no longer an independent prognostic factor after allowing for acute-stage infarct hypoperfusion volume. This study shows that crossed cerebellar diaschisis is a functional phenomenon that correlates with both stroke severity and infarct hypoperfusion volume and persists despite neurological recovery. Although acute-stage crossed cerebellar diaschisis has no prognostic value independent of acute-stage hypoperfusion volume, it might indicate the proportion of nutritional to nonnutritional perfusion at the infarct site and hence be useful in the evaluation of reperfusion therapies in the acute stage.

Nitric oxide and adenosine mediate vasodilation during functional activation in cerebellar cortex

Activation of the cerebellar parallel fibers (PF) releases glutamate and leads to depolarization of Purkinje cells and interneurons. These cells, in turn, release GABA. We have studied the role of glutamate, GABA, nitric oxide (NO) and adenosine in the increases in cerebellar cortex blood flow (BF crb) elicited by PF stimulation. In anesthetized rats (halothane 1%) the cerebellar vermis was exposed and the site was superfused with Ringer (37°C, pH 7.4). The PF were stimulated electrically (50–100 μA; 30 Hz) and the increases in BF crb were recorded using a laser-Doppler flowmeter. Field potentials were recorded using glass microelectrodes. During Ringer superfusion, PF stimulation increased BF crb by 58 ± 5% ( P < 0.001; analysis of variance; n = 6). Superfusion with the broad spectrum glutamate receptor antagonist kynurenic acid (Kyn; 5 mM) abolished the negative component of the field potential ( n = 4), a finding reflecting lack of depolarization of Purkinje cells and interneurons, and blocked the increase in BF crb ( P > 0.05 from Ringer; n = 6). In contrast, Kyn did not influence the increase in BF crb evoked by hypercapnia (pCO 2 55.4 ± 1.1 mmHg) or by superfusion with the NO donor SIN-1 (0.1, 1 mM; P > 0.05; n = 6). Superfusion with the adenosine receptor antagonist 8-sulphophenyltheophylline (8-SPT; 100 μM) reduced the elevation in BF crb by 45 ± 4% ( P < 0.05; n = 6) and co-application of 8-SPT and of the NO synthase inhibitor nitro- l-arginine ( l-NA; 1 mM) attenuated the vasodilation further (−82 ± 4% from Ringer; P < 0.01 from 8-SPT alone). The vasodilation elicited by SIN-1 ( n = 6) and the field potentials evoked by PF stimulation ( n = 4) were not affected by 8-SPT or by 8-SPT plus l-NA. The GABA receptor antagonist bicuculline (300 μM) produced the expected changes in the field potentials ( n = 4) but did not affect the vascular response to PF stimulation ( P . 0.05; n = 5). The data suggest that release of glutamate from PF leads to production of NO and adenosine in Purkinje cells and/or interneurons. NO and adenosine may mediate the vasodilation by diffusing toward resistance arterioles and producing smooth muscle relaxation.

Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study.

There has been debate as to whether essential tremor has a central origin and over the possible role of the inferior olivary nucleus in its genesis. We used positron emission tomography with radioactive water (H2(15)O) to detect abnormal patterns of cerebral activity associated with this condition, at rest, without tremor, and on posture when the tremor was present. At rest, cerebellar blood flow was significantly increased bilaterally in the group with essential tremor (30-40%) but no increased olivary activity was evident. Essential tremor during arm extension was associated with further abnormal increases in bilateral cerebellar and abnormal red nuclear activation. Again, no olivary overactivity was evident. Voluntary wrist oscillation in control subjects caused only ipsilateral cerebellar activation. We conclude that essential tremor is associated with abnormal bilateral overactivity of cerebellar and red nuclear connections but found no evidence of intrinsic overactivity of the inferior olivary nucleus, as evidenced by raised blood flow.

Cardiovascular and Cerebrovascular Effects of the Applied Valsalva Manoeuvre in Anaesthetized Neurosurgical Patients

We examined the effects of Valsalva's manoeuvre and its four phase on heart rate, central venous pressure (CVP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP), and laser Doppler cerebellar cortical blood flow (CBF). Brief Valsalva manoeuvres increased CVP and markedly decreased MAP. Cerebral perfusion pressure significantly (P < or = 0.01, Dunnett's test) decreased during phases 2 and 3 of the Valsalva manoeuvre. Cortical blood flow closely paralleled CPP; CBF decreased to 59% of control during phase 2 and to 57% of control during phase 3 of the Valsalva manoeuvre. The MAP, CPP, and CBF all returned to baseline levels during phase 4 (the overshoot phase) of the Valsalva manoeuvre, and were not significantly greater than control. No autoregulatory change in cerebrovascular resistance occurred throughout the Valsalva manoeuvre. These results suggest that brief Valsalva manoeuvres, as employed during neurosurgical procedures, mainly confirm venous haemostasis, but must be used cautiously due to the marked haemodynamic changes.

Crossed cerebellar hypoperfusion indicates the degree of uncoupling between blood flow and metabolism in major cerebral arterial occlusion.

In patients who have major cerebral arterial occlusive disease with low perfusion, a decrease in cerebral metabolism may be reflected by a reduction in contralateral cerebellar blood flow (crossed cerebellar hypoperfusion). This study was done to investigate whether comparison of the extent of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion could be used to estimate the degree of uncoupling of cerebral blood flow and metabolism on the basis of a single blood flow study. We used positron emission tomography before and after reconstructive vascular surgery to evaluate regional blood flow and oxygen metabolism in the cerebral and cerebellar cortexes of 11 patients with major cerebral arterial occlusive disease. Preoperatively these patients had cortical blood flow asymmetry in the middle cerebral artery territory. The degree of crossed cerebellar hypoperfusion had no relation to the extent of cerebral blood flow asymmetry but was significantly correlated with the extent of asymmetry in cerebral oxygen metabolism. The preoperative extent of asymmetry in the cerebral oxygen extraction fraction and the postoperative improvement of asymmetry in cerebral blood flow were correlated with the preoperative difference between the severity of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion. The difference between the extent of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion can be used to estimate the degree of uncoupling between blood flow and metabolism, which can in turn predict the postoperative improvement of cerebral blood flow asymmetry. We suggest that this approach may be a simple means of estimating the relative uncoupling between blood flow and metabolism from a single blood flow study in patients who have major cerebral arterial occlusive disease with low perfusion.

Endothelial injury following experimental subarachnoid hemorrhage in rats: effects on brain blood flow.

The leading cause of death and disability in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) is cerebral vasospasm, a persistent, progressive, and often irreversible constriction of cerebral arteries. A wide array of pathological changes occur in cerebral arteries following SAH, with endothelial injury being the earliest and most consistent one. Since intact endothelium modulates many reflexes that influence vascular tone, damage to them may represent a significant contributor to cerebral vasospasm. Changes in local cerebellar blood flow (LCBF) and pathological alterations in major cerebral arteries were studied and compared in rats at various time intervals following SAH. SAH induced by the subarachnoid injection of 0.3 ml of whole blood. Sham rats received a subarachnoid injection of 0.3 ml of isotonic saline. Except for an immediate but transient decrease, LCBF remained unchanged over a 3 day period following saline injection. Likewise, there were no pathological alterations in cerebral arteries of saline-injected rats. In contrast, the subarachnoid injection of whole blood produced significant changes in both LCBF and cerebral arteries. Within 30 minutes post-blood injection, LCBF became significantly decreased and remained so for 4 hours. However, within 24 hours, LCBF had returned to control levels where it remained for 3 days. Endothelial injury was observed in the basilar and middle cerebral arteries from 30 minutes through 4 hours, the same periods in which LCBF was significantly reduced. Within 24 hours, the time period in which LCBF had rebounded to control ranges, cerebral arteries showed no evidence of endothelial damage and resembled control cells. The results indicate a direct correlation between changes in LCBF and the structural integrity of endothelial cells in the early stages following SAH. The lack of chronically depressed LCBF (after 1 day) may be related to the quick structural repair of endothelium.

Olivopontocerebellar atrophy studied by positron emission tomography and magnetic resonance imaging

We examined 9 patients with olivopontocerebellar atrophy (OPCA) using positron emission tomography and magnetic resonance imaging (MRI). Regional cerebral blood flow and oxygen metabolism were compared with the findings in 10 normal age-matched volunteers. The volumes of the basis pontis and the cerebellar hemispheres were quantitated by MRI to assess the relationship between morphological changes of the pons or cerebellum and the cerebellar circulation and metabolism. In the patients with OPCA, cerebellar hemispheric blood flow and oxygen metabolism were significantly lower than in the normal volunteers. Pontine volume showed a significant correlation with the cerebellar blood flow and the metabolic rate of oxygen. In contrast, the cerebellar hemispheric volume showed no correlation with either of these parameters. Our results suggest that the disruption of pontocerebellar pathway may contribute to the reduction of both blood flow and oxygen metabolism in the cerebellum of OPCA and that detection of cerebellar circulatory impairment without marked cerebellar atrophy by neuroimaging may be suggestive of OPCA.