Intracardiac Thrombus Following Rivaroxaban Treatment in a Patient with Atrial Fibrillation Associated with Rheumatic Heart Disease.

We report a case of atrial fibrillation with rheumatic heart disease (RHD) who had intracardiac thrombus and cardiogenic cerebral embolism with rivaroxaban therapy. Intracardiac thrombus disappeared after switching from rivaroxaban to warfarin. Patients of RHD have the possibility of gradual progression of valvular disease even if they are old, so we need to distinguish nonvalvular atrial fibrillation from RHD before starting direct oral anticoagulants.

Relationship Between Infarct Volume and Prothrombin Time-International Normalized Ratio in Ischemic Stroke Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: In Japan, warfarin treatment at prothrombin time-international normalized ratio (PT-INR) of 1.60-2.60 is recommended for elderly patients with nonvalvular atrial fibrillation (NVAF). But it remains unknown whether PT-INR 1.60-1.99 has a similar effect on stroke severity as a value >2.0. The purpose of this study was to clarify the association between infarct volume and PT-INR levels.Methods and Results:The 180 patients (mean age, 76 years [SD, 10 years], 53% male) selected from 429 consecutive ischemic stroke patients admitted within 48 h of onset between 2004 and 2014 with NVAF were included. We classified them into 4 groups according to their PT-INR values on admission: no warfarin (NW), 129 patients; PT-INR <1.60 (poor control: PC), 29 patients; PT-INR 1.60-1.99 (low-intensity control: LC), 14 patients; and PT-INR ≥2.00 (high-intensity control: HC), 8 patients. Median (interquartile range: IQR) of infarct volume was 55 mL (IQR 14-175) in the NW, 42 mL (IQR 27-170) in the PC, 36 mL (IQR 6-130) in the LC, and 11 mL (IQR 0-39) in the HC groups. The infarct volume of the HC group was significantly smaller than in the other 3 groups, but no difference existed between the LC and PC groups or the LC and NW groups. CONCLUSIONS: Warfarin control at PT-INR of 1.60-1.99 is not effective for reducing the severity of ischemic stroke in NVAF patients.

P2Y12 Reaction Units and Clinical Outcomes in Acute Large Artery Atherosclerotic Stroke: A Multicenter Prospective Study.

AIMS: We aimed to determine the association between acute platelet reactivity and clinical outcome in acute ischemic stroke (AIS) or transient ischemic attack (TIA) with large-artery atherosclerosis (LAA). METHODS: In this prospective, 16-multicenter study, we enrolled AIS/TIA patients with LAA receiving clopidogrel. We assessed the association of P2Y12 reaction units (PRU) 24 hours after initiation of antiplatelets with the CYP2C19 genotype and recurrent ischemic stroke within 90 days, and the difference between acute (≤ 7 days) and subacute (8-90 days) phases. RESULTS: Among the 230 AIS/TIA patients enrolled, 225 with complete outcome data and 194 with genetic results were analyzed. A higher PRU was significantly associated with recurrent ischemic stroke within 90 days (frequency, 16%), and within 7 days (10%). Twenty-nine patients (15%) belonged to a CYP2C19 poor metabolizer group (CYP2C19＊2/＊2, ＊2/＊3, or ＊3/＊3). Multivariable receiver-operating characteristic analysis showed a greater area-under-the-curve (AUC) in predicting recurrence within 7 days, compared to 8-90 days (AUC, 0.79 versus 0.64; p=0.07), with a cut-off PRU of 254. Multivariable analysis showed high PRU (≥ 254), which had a comparable predictive performance for recurrent ischemic stroke within 7 days (odds ratio, 6.82; 95% CI, 2.23-20.9; p＜0.001) to the CYP2C19 poor metabolizer genotype. The net reclassification improvement, calculated by adding high PRU (≥ 254) to a model including the CYP2C19 poor metabolizer genotype in the prediction of recurrence within 7 days, was 0.83 (p＜0.001). CONCLUSIONS: Acute PRU evaluation possesses predictive value for recurrent ischemic stroke, especially within 7 days in AIS/TIA with LAA.

A multicenter brain perfusion SPECT study evaluating idiopathic normal-pressure hydrocephalus on neurological improvement.

PURPOSE: This study was designed to investigate the specific cerebral blood flow (CBF) pattern in patients with idiopathic normal-pressure hydrocephalus (iNPH) and a predictive value for shunt responsiveness in a multicenter study (Study of Idiopathic Normal-Pressure Hydrocephalus on Neurological Improvement: SINPHONI). METHODS: Eighty-four iNPH patients underwent shunt operations using MRI selection criteria from the SINPHONI and were subjected to CBF single photon emission computed tomography (SPECT). The perfusion patterns on SPECT were classified: anterior-dominant CBF reduction type (A type), posterior-dominant CBF reduction type (P type), and mixed or diffuse CBF reduction type (M type). The predictive value of the CBF pattern for favorable shunt outcome was evaluated. RESULTS: Favorable outcomes were obtained in 76% (64/84) of patients, and shunt responsiveness was achieved in 85% (71/84) of patients. Areas of severely reduced relative CBF were demonstrated around the corpus callosum and in the sylvian fissure area, which included the effects of dilatations of the ventricles and sylvian fissures and relatively increased perfusion in the medial and lateral frontal, parietal, and occipital areas at high convexity. Forty-nine (58%) cases were A type, 25 (30%) cases were M type, and 10 (12%) cases were P type. A, M, and P type cases exhibited 83, 84, and 90% positive predictive values for shunt responsiveness, respectively. Mean modified Rankin scale and Mini-Mental State Examination scores of the A type group were significantly better than those of other groups. CONCLUSION: The iNPH patients showed various patterns of CBF reduction, but there was no significant difference in the predictive value among the three patterns, though CBF reduction patterns may suggest a severe condition of iNPH.

[Progressive multifocal leukoencephalopathy in a patient with rheumatoid arthritis under salazosulfapyridine treatment].

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by JC virus (JCV) activation. We report an 85-years old man who had been diagnosed to have rheumatoid arthritis (RA) 1.5 years prior to diagnosis of PML, and had been treated with salazosulfapyridine (SASP). He developed weakness of the left upper limb, which progressed gradually for two months. A neurological examination on admission revealed severe palsy of the left upper limb without sensory disturbance, cognitive decline or gait disturbance. Brain MRI revealed white matter lesions in the right frontal lobe around the precentral gyrus. Cerebrospinal fluid (CSF) examination and peripheral lymphocyte counts were normal. HIV was ruled out serologically. There were no findings suggestive of malignancy. We suspected PML and stopped SASP. JCV-DNA was detected in CSF. There were enlarged nuclei positive with VP-1 immunostaining in the brain biopsy materials. Thus, the diagnosis of PML was definitive. Paralysis of the left upper limb began to improve one week after discontinuing SASP. Treatment with mefloquine and mirtazapine was initiated, but he developed severe interstitial pneumonia, which might be caused by mefloquine. Therefore, he underwent rehabilitation without medication. JCV-DNA became undetectable and white matter lesions decreased 6 months later. Paralysis improved and he had no problem with activities of daily living a year later. The risk factor for PML has changed over the last decade, and drugs such as biologics became significant risk factors for patients with autoimmune diseases. There are reports suggesting that systemic lupus erythematosus (SLE) and RA themselves might be independent risk factors for PML. Although there is no previous report of SASP inducing PML, SASP might be the culprit in our case. However, there is another possibility that SAPS and RA worked synergistically for the onset of PML.

Gait disturbance associated with white matter changes: a gait analysis and blood flow study.

To clarify the mechanisms underlying gait disturbance secondary to age-related white matter changes (ARWMC), cerebral perfusion was investigated during treadmill walking. Twenty subjects with extensive hyperintensities in the periventricular and deep white matter on T(2)-weighted magnetic resonance images (MRI) were recruited. The ARWMC subjects were classified into gait-disturbed (GD) and non-GD groups according to clinical criteria. All the subjects underwent gait analyses and cerebral perfusion measurements during both gait and rest by using single photon emission computed tomography. The GD group showed greater double support time/phase and stride width, and slower walking velocity, than the non-GD group. In an analysis of pooled data from all the subjects, gait-induced increases in cerebral perfusion were observed in the supplementary motor areas (SMA), lateral premotor cortex (PMC), primary motor and somatosensory areas, visual areas, basal ganglia and cerebellum. A between-group comparison of gait-induced perfusion changes showed relative underactivation of the SMA, thalamus and basal ganglia, together with relative overactivation of the PMC, in the GD group compared with the non-GD group. In a separate correlation analysis including all the subjects, as the double support phase was longer (that was, gait disturbance was more severe), the gait-induced perfusion changes were proportionally reduced in the SMA, visual cortex, and thalamus. The present study suggests that abnormalities in the basal ganglia-thalamo-cortical loops partly explain gait disturbance observed in a subset of subjects with ARWMC.

Impairment of the cortical GABAergic inhibitory system in catatonic stupor: a case report with neuroimaging.

We report the case of a 32-year-old patient who presented with catatonic stupor during the course of acute aseptic encephalitis involving the right frontotemporal area. Flumazenil-PET performed during the stupor indicated decreased benzodiazepine receptor binding in the right frontotemporal area where glucose metabolism was preserved as revealed by FDG-PET. An injection of diazepam immediately ameliorated catatonic symptoms and reduced widespread high amplitude slow EEG activities with right frontotemporal predominance. Compared with a SPECT study performed a week earlier, there was no abnormal right-sided anteriorly predominant cerebral hyperperfusion after injection of diazepam. While neither flumazenil- nor FDG-PET could be repeated, and with the caveat that generalized convulsions occurred initially and epilepsia partialis continua was present for two weeks starting on the 23rd day after illness onset, these findings suggest that in our case the presentation with catatonic stupor may be related to impairment of the cortical GABAergic inhibitory system.

[Case of a 30-year history of PARK6 --findings from functional imaging of the brain].

We have reported a case of autosomal recessive juvenile parkinsonism PARK6 with a 30-year history. She developed tremor of right lower limb at the age of 23. At the age of 28, she received a clinical diagnosis of early-onset Parkinson's disease. She showed clinical improvements by the treatment with trihexyphenidyl, but symptoms showed slow progression over the subsequent years. L-DOPA therapy was introduced at the age of 42, and five years later, L-DOPA-induced dyskinesia developed. Dystonia, diurnal fluctuation and sleep benefit were absent. She carried a homozygous missense mutation in PINK1 gene, and was diagnosed as PARK6. The brain MRI did not show apparent abnormality. 18F-FDG-positron emission topography (PET) displayed normal uptake in the brain, suggesting normal glucose metabolism. PET imaging with a dopamine D2 receptor ligand 11C-raclopride revealed that postsynaptic 11C-raclopride uptake was normal in the bilateral putamen. After the introduction of pramipexisol, she showed clinical improvements. L-DOPA-induced dyskinesia disappeared with the gradual tapering and withdrawal of L-DOPA. In this PARK6 case, postsynaptic D2 receptors of the nigro-striatal dopaminergic neurons were thought to be maintained despite a long disease history.

Quantification of nicotinic acetylcholine receptors in Parkinson's disease with (123)I-5IA SPECT.

We quantified in vivo brain nicotinic acetylcholine receptor (nAChR) distributions in patients with Parkinson's disease (PD) and evaluated correlations between nAChR distributions and clinical variables of the patients, especially dopaminergic medications. Ten patients with PD without dementia underwent 5-(123)I-iodo-3-(2(S)-azetidinylmethoxy)pyridine ((123)I-5IA) single photon emission computed tomography (SPECT) and the data were compared with those of 10 age-matched healthy volunteers. Correlation analyses between (123)I-5IA distribution volumes (DVs) in each brain region and clinical variables of the patients were also performed. The PD group showed a statistically significant decrease (20-25%) in the brainstem and frontal cortex as compared with the control group. Although age, duration of disease, daily dose of levodopa, duration of PD medication use, and scores on the motor section of Unified Parkinson's Disease Rating Scale were not significantly correlated with DV values in any brain regions, high daily doses of dopamine agonist showed a significant negative correlation with DVs in the cerebellum, and temporal, parietal and occipital cortices. These findings suggest that patients with PD without dementia can show reductions especially in the brainstem and frontal cortex. They also suggest that dopamine agonists can have a negative influence on the distribution of nAChRs.

Decreased cerebral blood flow and prognosis of Alzheimer's disease: a multicenter HMPAO-SPECT study.

PURPOSE: To determine the usefulness of brain perfusion SPECT for evaluating the severity and progression of Alzheimer's disease (AD). METHODS: Eighty-four AD patients were included. At entry, 99mTc-HMPAO-SPECT, the Mini Mental State Examination (MMSE), Mental Function Impairment Scale (MENFIS), and the Raven Colored Progression Matrix (RCPM) were performed for all 84 patients. During the follow-up periods, two individual MMSE evaluations in 34 patients, two MENFIS evaluations in 30 patients, and two RCPM evaluations in 20 patients were performed. Based on the regions of decreased cerebral blood flow demonstrated on 3D-SSP images of SPECT, the cases were classified as type A (no decrease), type B (decreased blood flow in the parietal or temporal lobe), type C (decreased blood flow in the frontal lobe and parietal or temporal lobe), type Pc (decreased blood flow in posterior cingulate gyrus only), and "other types". The types of decreased blood flow, scores on neuropsychological evaluations, and symptom progression were analyzed. RESULTS: The MENFIS, MMSE, and RCPM scores were poorest in type C patients at entry. The degree of decrease of these scores during the follow-up periods was also greatest in type C. The greatest difference between patients with and without rapid progression in SPECT data of the mild AD patients (MMSE score > or = 24) was in the frontal lobe. CONCLUSION: Decreased blood flow in the frontal lobe of AD patients is correlated not only with reduced cognitive function at the time of the evaluation but with rapid progression in the subsequent clinical course.

A case of recanalization of innominate artery and right middle cerebral artery embolism due to cardiogenic cerebral infarction with anticoagulation therapy.

An 80-year-old woman had an aortic valve replacement 1 month before admission and took warfarin for transient atrial fibrillation. She developed a disturbance of consciousness and left hemiplegia. On admission, the right radial artery was slightly palpable. Head MRI images showed a hyper-intense area in the right middle cerebral artery territory. MRA images showed an occlusion of the right M1 distal site and decreased signal at the right internal carotid artery. Contrast CT images of the ascending aorta showed an embolus in the innominate artery. She was diagnosed with an innominate artery saddle embolus and occlusion of the right cerebral artery due to cardiac embolism. She was treated with a heparin infusion and warfarin. She recovered consciousness and from hemiplegia gradually. Recanalization of the innominate artery and right cerebral artery was confirmed. In cases where the radial artery is slightly palpable, it is necessary to consider an innominate artery saddle embolus in addition to aortic dissection.

Neural mechanism of residual inhibition of tinnitus in cochlear implant users.

Residual inhibition is a transient suppression of tinnitus after auditory stimulation has stopped. We used positron emission tomography to study brain regions underlying residual inhibition in three tinnitus patients with cochlear implants and six normal hearing controls. Regional cerebral blood flow was measured and compared under two conditions: with tinnitus and during the residual inhibition of tinnitus. The right anterior middle and superior temporal gyri (Brodmann areas 21 and 38) were activated during residual inhibition, while the right cerebellum was activated during tinnitus perception in the tinnitus patients. No significant activation was observed in the normal controls. Our results suggest that tinnitus and residual inhibition are related to cortical networks of auditory higher-order processing, memory and attention.

Frontal nonconvulsive status epilepticus manifesting somatic hallucinations.

Somatic hallucinations are subjective experience of false, strange sensations of things occurring in or to the body. They can be seen in psychotic disorders, but have not been well described as an ictal psychosis in patients with nonconvulsive status epilepticus (NCSE) of frontal origin. We reported a 69-year-old woman who had NCSE of frontal origin manifesting prolonged somatic hallucinations mimicking a psychiatric disorder and initially treated as such. Ictal EEG revealed the frontal focus and ictal single-photon emission computed tomography (SPECT) showed the activation, not only in the frontal area but also in the parietal area as the projected regions, both of which might be associated with the development of her symptoms. She also had two generalized tonic-chronic seizures out of psychosis. Her psychosis and ictal rhythmic discharges on EEG ceased with valproate and she has since remained free from the symptoms. The current case suggests that long-lasting somatic hallucinations could be an ictal psychosis in frontal NCSE and thus an EEG study is needed for an early diagnosis and treatment.

Detection of misery perfusion with split-dose 123I-iodoamphetamine single-photon emission computed tomography in patients with carotid occlusive diseases.

BACKGROUND AND PURPOSE: Patients with carotid occlusive disease and stage 2 cerebral hemodynamic failure, characterized by an increased oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) and otherwise known as misery perfusion, have a high risk of cerebral ischemia and subsequent stroke. In clinical practice, the detection of patients with misery perfusion through the use of widely available, noninvasive, and cost-effective modalities such as single-photon emission computed tomography (SPECT) is extremely important. METHODS: We evaluated the relationships between the regional hemodynamic status of cerebral circulation, measured with split-dose [123I] N-isopropyl-p-iodoamphetamine SPECT (123I-IMP SPECT) and an acetazolamide challenge, and hemodynamic parameters, including OEF measured with PET, in 27 patients with both unilateral and bilateral carotid occlusive diseases. RESULTS: A significant negative correlation was found between the SPECT-measured cerebrovascular reserve after acetazolamide administration and both the PET-measured OEF and cerebral blood volume. Neither the cerebrovascular reserve nor the cerebral blood flow index, when expressed as a SPECT-measured cerebrum-to-cerebellum ratio, was useful for detecting lesions with an elevated OEF. However, a combination of the cerebrovascular reserve and cerebral blood flow index showed high sensitivity, specificity, and positive predictive value for the detection of misery perfusion. CONCLUSIONS: Our study suggests that split-dose 123I-IMP SPECT with an acetazolamide challenge could be useful for screening patients with misery perfusion in carotid occlusive diseases.

Assessment of acetazolamide reactivity in cerebral blood flow using spectral analysis and technetium-99m hexamethylpropylene amine oxime.

Cerebral blood flow (CBF) can be quantified noninvasively using the brain perfusion index (BPI), determined from radionuclide angiographic data generated with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO). Previously, the BPI has been calculated using graphical analysis (GA); however, the GA method is greatly affected by the first-pass extraction fraction and retention fraction, which are not only variable, but lower in cases with an increased CBF, such as after the administration of acetazolamide. Thus, GA-calculated BPI values (BPIG) may not reflect the absolute CBF. The objective of this study was to use the spectral analysis of radionuclide angiographic data collected using 99mTc-HMPAO to examine changes in the BPI after the administration of acetazolamide. We studied the CBF of both cerebral hemispheres in six healthy male volunteers; the BPI was measured at rest and after the intravenous administration of 1 g of acetazolamide. In all participants, an H215O positron emission tomography (PET) examination was also performed, and the spectral analysis-calculated BPI values (BPIS) and BPIG values were compared with the actual CBF measured using H215O PET (mCBFPET). The BPIS was 1.070 +/- 0.051 (mean +/- SD) at rest and 1.497 +/- 0.098 after acetazolamide; the corresponding BPIG values were 0.646 +/- 0.073 and 0.721 +/- 0.107. The BPIS values were significantly correlated with the mCBFPET values, whereas the BPIG values were not. According to the BPIS values, the increase in BPI after the intravenous administration of acetazolamide was 40.1 +/- 8.4%, as opposed to an increase of only 11.3 +/- 6.5% according to the BPIG values. These results suggest that the spectral analysis of 99mTc-HMPAO-generated data yields a more reliable BPI than GA for the quantification of CBF after acetazolamide administration.

Sensory stimulation accelerates dopamine release in the basal ganglia.

We report herein the modulation of dopamine release in the basal ganglia during peripheral electrical stimulation in animals. The endogenous dopamine release during electrical stimulation was measured in anesthetized cats by positron emission tomography (PET) using the D2 receptor agonist [11C]-raclopride. Binding potential (BP) parametric maps were calculated using a simplified reference region model. The regional dopamine release evoked by electrical stimulation was estimated both by region of interest (ROI) analysis and statistical parametric mapping (SPM 99). Both ROI analysis and statistical parametric mapping showed significant release of endogenous dopamine in the nucleus accumbens and the striatum contralateral to the stimulated side as compared to the resting condition as well as the ipsilateral side. Accordingly, we suggest that the activity of the dopaminergic neurons in the midbrain projecting to the nucleus accumbens and the striatum is modulated by the input from the afferent nerves. This provides an in vivo evidence for the importance of the basal ganglia in the processing of peripheral information required for normal movement. This may also explain the clinically observed sensory system abnormalities in patients with movement disorders.

Quantification of the heterogeneity of cerebral blood flow in vascular dementia.

BACKGROUND: In vascular dementia (VaD), assessment of cerebral blood flow by single photon emission computed tomography (CBF SPECT) has been used to detect a patchy decrease of blood flow or a frontal reduction. In addition to reduced blood flow, the heterogeneous distribution of cerebral blood flow is often observed in VaD. However, no objective method to evaluate the heterogeneity has been established. In this study, we applied three-dimensional fractal analysis (3D-FA) to CBF SPECT images as a method for assessing the heterogeneity of the cerebral blood flow distribution in VaD. SUBJECTS AND METHODS: The subjects included 18 patients with a diagnosis of VaD (aged 69.7 +/- 8.3) based on neuropsychological testing and imaging findings and 18 age-matched controls (aged 66.9 +/- 10.3). CBF SPECT images were obtained with (99m)Tc-hexamethyl propyleneamine oxime. On the reconstructed images, we obtained a linear regression equation between the cut-off values (from 35 to 50 %) and the number of voxels with a radioactivity exceeding the cut-off value transformed into natural logarithms, and then calculated the fractal dimension from the slope of the regression line thus obtained. The Mini-Mental State Examination (MMSE) was used to evaluate cognitive function. RESULTS: The fractal dimensions were 1.084 +/- 0.153 and 0.853 +/- 0.062 (mean +/- SD) in the VaD and control groups, respectively. The fractal dimension was significantly greater in the VaD group than in the control group (p < 0.0001). A significant negative correlation was observed between the fractal dimension and the MMSE score in the VaD group (r = 0.871, p < 0.0001). CONCLUSIONS: Because the CBF SPECT images of VaD patients showed a higher fractal dimension, these images were quantitatively more heterogeneous than those of age-matched controls. In the VaD group, cognitive function was shown to decline as the fractal dimension increased and images became more heterogeneous.

Prognostic value of subacute crossed cerebellar diaschisis: single-photon emission CT study in patients with middle cerebral artery territory infarct.

BACKGROUND AND PURPOSE: Although chronic-stage crossed cerebellar diaschisis (CCD) is reported to be associated with the neurologic state or clinical improvement after infarct, the prognostic value of early-stage CCD remains controversial. Our aim was to determine whether measurements of CCD in the acute and subacute stages obtained at single-photon emission CT (SPECT) facilitate the prediction of stroke outcome. METHODS: The pattern of cerebral blood flow changes after the occurrence of acute middle cerebral artery ischemia with severe cortical symptoms was examined by using technetium 99m-hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) SPECT. Fifteen patients (mean age, 73 years +/- 8 [SD]) with unilateral ischemia were examined in the early subacute stage (10 days +/- 5). In 11 patients, SPECT was performed in both the acute (16 hours +/- 10) and subacute stages. From the total counts obtained from each cerebellar hemisphere, the asymmetry index (AI) was calculated as follows: [(value in unaffected hemisphere--value in affected hemisphere)/value in unaffected hemisphere] x 100. Clinical outcome (at 60 days) was assessed by means of the Scandinavian Stroke Scale (SSS) and Barthel Index (BI). RESULTS: AIs in the acute stage and clinical outcome (ie, SSS and BI scores) showed no significant correlation, but the severity of AI in the early subacute stage correlated significantly with both the final SSS (r = -0.69; P <.01) and BI scores (r = -0.82; P <.01). CONCLUSION: Cerebellar hypoperfusion detected at (99m)Tc-HMPAO SPECT in the early subacute stage in patients with supratentorial infarct indicates a worse clinical outcome.

Prominent matched hypoperfusion in an intact cerebellum after a solitary middle cerebellar peduncle infarct.

We examined the cerebellar metabolism of a 61-year-old man with a small infarct in the left middle cerebellar peduncle and an intact cerebellum. Positron emission tomographic images obtained 28 days after onset showed prominent hypoperfusion and hypometabolism (almost 50% below the normal level) in the left cerebellar hemisphere. This case report shows that neural deafferentation may cause prominent hypometabolism without morphologic changes in the cerebellum. An arrest in synaptic activity may be the most important factor for the adaptive decrease in oxygen metabolism seen in ischemic brain.