M C Austin

Dystonia, clinical lateralization, and regional blood flow changes in temporal lobe seizures

We analyzed the lateralizing value of ictal dystonia and head-turning in temporal lobe epilepsy, and sought the biologic basis of these clinical signs by studying the regional changes in perfusion with ictal single-photon emission computed tomography (SPECT). We identified unilateral temporal lobe epilepsy in 40 of 42 patients undergoing evaluation for temporal lobe surgery, and with ictal SPECT all 40 showed striking hyperperfusion of the epileptogenic temporal lobe. Twenty-five of the 40 patients showed unilateral or predominantly unilateral upper limb dystonia, which was opposite the epileptic temporal lobe in all cases. Analysis of regional count ratios in cases with ictal dystonia, compared with those without, showed significant changes only in the basal ganglia. Specifically, we found that ictal dystonia was associated with a relative increase in perfusion of the basal ganglia opposite the dystonic limb. Although we found 26 cases with head-turning, the sign was of no lateralizing value, even when only those with major or “tonic” versions (n = 11) were analyzed. Slight increases in cortical blood flow on the side opposite the direction of version were associated with head-turning, irrespective of the side of seizure focus. In clinical practice, ictal SPECT is a highly accurate aid in the lateralization of temporal lobe foci, in addition to providing a new method to investigate the pathophysiology of clinical signs in focal seizures.

Patterns of postictal cerebral blood flow in temporal lobe epilepsy Qualitative and quantitative analysis

We used single-photon emission computed tomography (SPECT) to study postictal cerebral blood flow (CBF) in 51 patients with temporal lobe epilepsy. There were 78 seizures studied, 77 by early postictal injection of Tc-99m HMPAO (delay from seizure onset = 4.3 ± 4.5 min) and one by ictal injection. Increased focal temporal lobe uptake, predominantly confined to the anteromesial region, was present in 83% and declined rapidly over 5 minutes. Reduced activity in the lateral temporal lobe accompanied the mesial increase in 80% of studies, extending over much of the ipsilateral hemisphere and closely associated with the degree and extent of postictal EEG slow waves. These patterns enabled correct seizure localization by blinded analysis in 69% (31/45) of the patients with a unilateral EEG focus. The remainder showed bilateral or no changes. One of six patients with bitemporal EEG foci had unilateral perfusion changes. The positive predictive value for the correct localization of a unilateral focus by postictal SPECT was 97% (31/32). Postictal CBF imaging with SPECT can be used to support noninvasive electrographic localization and may decrease the need for invasive electrode studies.

SPECT in the localisation of extratemporal and temporal seizure foci.

The yield of ictal, postictal, and interictal SPECT was compared in the localisation of seizure foci in 177 patients with partial epilepsy. In 119 patients with known unilateral temporal lobe epilepsy ictal SPECT (97% correct localisation) was superior to postictal SPECT (71% correct), which was better than interictal studies (48% correct). Similarly, in cases of known or suspected extratemporal epilepsy the yield of ictal SPECT studies was high (92%). By contrast, the yield of postictal studies was much lower (46%) and usually only very early postictal studies were diagnostic. Interictal SPECT was of little value. The accuracy of ictal SPECT in localising temporal lobe seizures is now well established. Extratemporal seizures are often brief and difficult to localise. This report shows that ictal SPECT also has a high diagnostic yield in a wide range of extratemporal epilepsies. The brevity of many extratemporal seizures means that true ictal SPECT examinations can be difficult to achieve, but the high diagnostic yield justifies the special organisational effort needed to obtain such studies.

Postictal switch in blood flow distribution and temporal lobe seizures.

The ictal increase of regional cerebral blood flow has yet to be fully utilised in the investigation of focal seizures. Although single photon emission tomography (SPECT) is being increasingly used in the localisation of epileptic foci, the evolution and time courses of the peri-ictal perfusion changes have yet to be clarified. We performed serial SPECT studies in the interictal, ictal and immediate postictal states in 12 patients with refractory temporal lobe epilepsy to define the patterns and duration of peri-ictal cerebral blood flow changes. Visual analysis showed a constant pattern of unilateral global increases in temporal lobe perfusion during seizures which suddenly switched to a pattern of relative mesial temporal (hippocampal) hyperperfusion and lateral temporal hypoperfusion in the immediate postictal period. Quantitative analysis confirmed the visual assessment. Lateral temporal cortex ictal/normal side to side ratios were increased by mean 35.1% (95% confidence interval 21.8% to 48.4%) more in the ictal studies than in the interictal studies and mesial temporal cortex ratios increased by mean 30.8% (22.4% to 39.2%). In the postictal state, however, lateral temporal ratios were reduced by mean 7.7% (-15.8% to 0.4%) compared with interictal values, whereas mesial temporal perfusion was maintained compared with the interictal studies. These observations provide critical information for interpreting scans which can be used in the localisation of epileptic foci. This postictal switch in blood flow patterns may reflect the underlying metabolic processes of neuronal activation and recovery and have implications for understanding the neurobiology of human epileptic seizures.

Parietal lobe epilepsy Clinical features and seizure localization by ictal SPECT

We studied clinical and ictal single-photon emission computed tomography (SPECT) features in 14 patients with parietal lobe epilepsy, nine of whom had structural parietal lobe lesions. Thirteen patients had simple partial seizures of somatosensory (eight), psychic (four), and motor (nine) types. Complex partial seizures (CPS) occurred in seven patients; six were psychoparetic (prominent staring, relative immobility) and one had hyperkinetic activity. Seizures lasted 7 to 110 seconds; 99mTc-HMPAO (hexamethylpropylene amine oxime) was injected ictally, 7 to 89 seconds from seizure onset and 0 to 74 seconds (mean, 21.0 ± 24.4 seconds) before seizure termination. Ictal SPECT demonstrated focal areas of parietal hyperperfusion in all 14 cases and corresponded with sites of the structural lesions. Parietal hyperperfusion was anterior in eight, posterior in four, and diffuse in two. Quantitative analysis revealed increases in parietal side-to-side perfusion ratios on ictal compared with interictal scans of 11 to 51% (mean, 25.5 ± 14.4%). Ictal SPECT localization correlated with two main clinical seizure patterns: an anterior syndrome characterized by sensorimotor manifestations and a posterior syndrome characterized by CPS of the psychoparetic type. Ictal SPECT is helpful for localization of parietal seizures. Parietal hyperperfusion is discrete and short-lived, demanding true ictal injections for diagnostic studies.

Reperfusion after thrombolytic therapy in ischemic stroke measured by single-photon emission computed tomography.

Background and Purpose We used 99mTc-hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) to study cerebral perfusion in patients treated with streptokinase for acute ischemic stroke in an open and prospective study. Our primary aims were (1) to compare the extent of reperfusion between patients who had received thrombolytic therapy and a control group studied during the same period who were ineligible to receive such therapy and (2) to determine if, among all patients, reperfusion led to improved outcome. Methods Fifty-seven patients (22 treated with streptokinase) had two SPECT studies performed, the first before streptokinase administration and the second 24 hours later. Results On the first SPECT study hypoperfusion was present in the middle cerebral artery or anterior cerebral artery territories in 40 patients (17 treated with streptokinase). Patients in the treatment and control groups with initial hypoperfusion on SPECT were well matched for the volume of the perfusion defect and the severity of neurological deficit. A greater number of patients who received streptokinase developed at least partial reperfusion (streptokinase, 65%; control, 52%) on the second study but not significantly so (P=.43). Similarly, the proportion of each hypoperfused region that reperfused (P=.74) and the reduction in the size of the perfusion defect (P =.06) were higher in the streptokinase group but did not reach statistical significance. When all patients were considered, those who did not reperfuse had higher mortality rates (P=.008), less neurological improvement (P=.016), and more functional disability (P < .001) than patients who had reperfusion or normal perfusion initially. Conclusions These findings suggest that at least some reperfusion during the first 48 hours of ischemic stroke is a common natural occurrence and is of prognostic significance. The observed trend toward better reperfusion indexes among patients treated with streptokinase is encouraging, but larger controlled trials are required to answer this definitively.

Ictal postictal and interictal single-photon emission tomography in the lateralization of temporal lobe epilepsy

Single-photon emission tomography (SPET) using radioligands that are fixed on first pass through the cerebral circulation shows distinctive and rapidly changing blood flow patterns accompanying temporal lobe seizures. We sought to determine the optimal time to perform SPET studies for clinical seizure lateralization in temporal lobe epilepsy. Interictal, ictal and postictal SPET scans of 73 consecutively studied patients with unilateral temporal lobe epilepsy were read by three blinded observers to assess the accuracy of lateralization in each condition. The blinded observers correctly identified the side of focus in 97% of ictal studies, 72% of postictal studies and 50% of interictal studies. No incorrect scores were made in the ictal studies, whilst 5% of postictal and 12% of interictal studies were lateralized to the wrong side. Inter-observer agreement was best with the ictal studies. The dramatic perfusion changes of ictal SPET provide consistent, reliable and easily interpretable information that is superior to that provided by interictal and postictal studies. Injection of ligand during seizures is therefore the method of choice for SPET to aid the non-invasive lateralization of temporal seizure foci.

Changes in cerebral tissue perfusion during the first 48 hours of ischaemic stroke: relation to clinical outcome.

BACKGROUND--One major therapeutic strategy to minimise the extent of infarction after ischaemic stroke is to improve early reperfusion using thrombolytic agents. However, reperfusion may be hazardous and the period during which reperfusion may have a beneficial effect on tissue and clinical outcome is not known. METHODS--Fifty three patients were studied with serial cerebral perfusion (99mTcHMPAO SPECT) during the first 48 hours of ischaemic stroke to determine if changes in tissue perfusion during this time were prognostically significant. Single and multiple linear regression non-parametric analyses were used to include other factors during the same period which may influence outcome. RESULTS--In univariate analysis age, neurological score at admission, SPECT perfusion defect size in the first 24 hours, and percentage change in cerebral tissue perfusion at 24-48 hours (all P < 0.01) correlated significantly with the Barthel score at three months. In multiple linear regression analysis only age (P < 0.01) and percentage change in cerebral tissue perfusion at 24-48 hours (P < 0.01) provided independent prognostic information at three months. CONCLUSIONS--Changes in cerebral tissue perfusion during the first 48 hours of ischaemic stroke are significant outcome predictors and therapeutic effort aimed at increasing perfusion during this period seem to be justified.

Sensitivity and Specificity of 99mTc-HMPAO SPECT Cerebral Perfusion Measurements During the First 48 Hours for the Localization of Cerebral Infarction

BACKGROUND AND PURPOSE There is no routinely used method for imaging the location of the extent and severity of cerebral tissue perfusion changes during the first hours of ischemic stroke, the period during which therapeutic intervention is most likely to be successful. Cerebral perfusion measurements with single-photon emission CT (SPECT) may potentially provide this information rapidly and noninvasively. In this study, the sensitivity and specificity of 99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT cerebral perfusion measurements during the first 48 hours of cerebral ischemia for the localization of cerebral infarction were determined. METHODS One hundred and four patients with acute ischemic stroke underwent 99mTc-HMPAO SPECT and CT scanning during the first 48 hours. In each patient, the location of the SPECT perfusion abnormality was compared with the location of infarction on a second brain CT acquired at a mean of 8 days after stroke. RESULTS During the first 48 hours of ischemic stroke, the sensitivity of 99mTc-HMPAO SPECT in locating the site of infarction was 79% (110/139), and the specificity was 95% (362/381). SPECT was more sensitive in the localization of the vascular territory of cortical infarction (sensitivity, 93%) than pure subcortical infarcts (sensitivity, 47%). During the first 48 hours, SPECT was significantly more sensitive than brain CT (sensitivity of brain CT during the first 48 hours, 35%; P < .001, Mann-Whitney U test). CONCLUSIONS HMPAO SPECT measurement provides a widely available and practical technique of locating cerebral ischemia acutely and demonstrates high sensitivity and specificity within the first 48 hours for the localization of the vascular territory of cerebral infarction. It is most sensitive for cortical ischemia but is limited by its resolution in the subcortex, particularly of white matter perfusion changes.

Early reperfusion in the 'spectacular shrinking deficit' demonstrated by single-photon emission computed tomography.

The “spectacular shrinking deficit” (SSD) refers to a syndrome of profound hemispheric ischemia that resolves rapidly over hours to days, leaving patients with minimal residual neurologic deficits. The SSD is postulated to result from rapid embolic lysis, fragmentation, and migration along the internal carotid/middle cerebral artery axis, leading to restored tissue perfusion before irreversible tissue damage has occurred. We performed serial single-photon emission computed tomographic (SPECT) cerebral perfusion measurements during the first 48 hours in 36 patients admitted with major hemispheric ischemia, to compare the cerebral perfusion changes between patients who developed SSD (n = 5) and those who did not (n = 31). The two groups were similar for severity of neurologic deficit, time of SPECT study, and size of perfusion defect on the SPECT images. Patients with SSD were younger (p = 0.02, Mann-Whitney U), demonstrated significantly greater tissue reperfusion during the first 48 hours (p < 0.011, and had smaller infarcts on CT (p = 0.02). This syndrome provides an opportunity to understand the mechanism by which early reperfusion may result in early tissue salvage and clinical recovery.