Clinical use of ictal SPECT in secondarily generalized tonic-clonic seizures.

Partial seizures produce increased cerebral blood flow in the region of seizure onset. These regional cerebral blood flow increases can be detected by single photon emission computed tomography (ictal SPECT), providing a useful clinical tool for seizure localization. However, when partial seizures secondarily generalize, there are often questions of interpretation since propagation of seizures could produce ambiguous results. Ictal SPECT from secondarily generalized seizures has not been thoroughly investigated. We analysed ictal SPECT from 59 secondarily generalized tonic-clonic seizures obtained during epilepsy surgery evaluation in 53 patients. Ictal versus baseline interictal SPECT difference analysis was performed using ISAS (http://spect.yale.edu). SPECT injection times were classified based on video/EEG review as either pre-generalization, during generalization or in the immediate post-ictal period. We found that in the pre-generalization and generalization phases, ictal SPECT showed significantly more regions of cerebral blood flow increases than in partial seizures without secondary generalization. This made identification of a single unambiguous region of seizure onset impossible 50% of the time with ictal SPECT in secondarily generalized seizures. However, cerebral blood flow increases on ictal SPECT correctly identified the hemisphere (left versus right) of seizure onset in 84% of cases. In addition, when a single unambiguous region of cerebral blood flow increase was seen on ictal SPECT, this was the correct localization 80% of the time. In agreement with findings from partial seizures without secondary generalization, cerebral blood flow increases in the post-ictal period and cerebral blood flow decreases during or following seizures were not useful for localizing seizure onset. Interestingly, however, cerebral blood flow hypoperfusion during the generalization phase (but not pre-generalization) was greater on the side opposite to seizure onset in 90% of patients. These findings suggest that, with appropriate cautious interpretation, ictal SPECT in secondarily generalized seizures can help localize the region of seizure onset.

Cortical and subcortical networks in human secondarily generalized tonic-clonic seizures.

Generalized tonic-clonic seizures are among the most dramatic physiological events in the nervous system. The brain regions involved during partial seizures with secondary generalization have not been thoroughly investigated in humans. We used single photon emission computed tomography (SPECT) to image cerebral blood flow (CBF) changes in 59 secondarily generalized seizures from 53 patients. Images were analysed using statistical parametric mapping to detect cortical and subcortical regions most commonly affected in three different time periods: (i) during the partial seizure phase prior to generalization; (ii) during the generalization period; and (iii) post-ictally. We found that in the pre-generalization period, there were focal CBF increases in the temporal lobe on group analysis, reflecting the most common region of partial seizure onset. During generalization, individual patients had focal CBF increases in variable regions of the cerebral cortex. Group analysis during generalization revealed that the most consistent increase occurred in the superior medial cerebellum, thalamus and basal ganglia. Post-ictally, there was a marked progressive CBF increase in the cerebellum which spread to involve the bilateral lateral cerebellar hemispheres, as well as CBF increases in the midbrain and basal ganglia. CBF decreases were seen in the fronto-parietal association cortex, precuneus and cingulate gyrus during and following seizures, similar to the 'default mode' regions reported previously to show decreased activity in seizures and in normal behavioural tasks. Analysis of patient behaviour during and following seizures showed impaired consciousness at the time of SPECT tracer injections. Correlation analysis across patients demonstrated that cerebellar CBF increases were related to increases in the upper brainstem and thalamus, and to decreases in the fronto-parietal association cortex. These results reveal a network of cortical and subcortical structures that are most consistently involved in secondarily generalized tonic-clonic seizures. Abnormal increased activity in subcortical structures (cerebellum, basal ganglia, brainstem and thalamus), along with decreased activity in the association cortex may be crucial for motor manifestations and for impaired consciousness in tonic-clonic seizures. Understanding the networks involved in generalized tonic-clonic seizures can provide insights into mechanisms of behavioural changes, and may elucidate targets for improved therapies.

The role of single photon emission computed tomography brain imaging with 99mTc-bicisate in the localization and definition of mechanism of ischemic stroke.

99mTc-bicisate (99mTc-ECD) is a new brain perfusion imaging agent formulated from a radiochemically stable kit (Neurolite). A multicenter trial was conducted to determine the sensitivity and specificity of single photon emission computed tomography (SPECT) imaging with 99mTc-bicisate in the localization of ischemic stroke; 170 subjects were enrolled, 128 patients with stroke and 42 controls. Imaging results from 148 subjects (107 stroke patients and 41 controls) were considered evaluable. In the evaluable subjects, SPECT brain imaging with 99mTc-bicisate (21.0 +/- 2.5 mCi) was interpreted without clinical information and was compared with a final assessment using all clinical, diagnostic, and laboratory procedures except the 99mTc-bicisate SPECT results. 99mTc-bicisate was safe and well-tolerated. SPECT imaging with 99mTc-bicisate demonstrated a specificity of 98% and a sensitivity of 86% for localization of strokes (kappa, 0.75; 95% confidence interval, 0.64-0.86). Results were unchanged over time and were similar for all stroke mechanisms except for lacunar disease (sensitivity, 58%). In a secondary analysis, a normal image or small, deep (e.g., subcortical) perfusion defect was highly predictive of a lacunar mechanism. Defects involving the cortical surface were strongly associated with nonlacunar mechanisms. SPECT imaging with 99mTc-bicisate is a sensitive marker in the localization of perfusion defects associated with ischemic stroke and may assist in the determination of the underlying mechanism of a stroke.

Comparison of single-photon emission computed tomography with [123I]iodoamphetamine and xenon-enhanced computed tomography for assessing regional cerebral blood flow.

Regional CBF (rCBF) images obtained from xenon-enhanced computed tomography (XeCT) and single-photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine (IMP) done with a rotating gamma-camera were compared in nine patients. Both XeCT and SPECT/IMP demonstrated flow abnormalities at all sites of infarction identified by CT, while detecting reduced rCBF in areas normal by CT in eight of the nine patients. All areas that were abnormal on XeCT were abnormal on the comparable SPECT/IMP images. The major advantages of XeCT are its greater resolution and potential for noninvasive quantitation of rCBF, while the major advantage of SPECT/IMP is its visualization of the entire brain on transverse, coronal, and sagittal sections.

Evaluation of regional cerebral blood flow in massive intracerebral calcifications.

Fahr's disease is histopathologically characterized by massive bilateral calcifications of the cerebral basal ganglia, the dentate nuclei of the cerebellum and both the cerebral and cerebellar cortices. We report a case of Fahr's disease in which a 99mTc-hexamethyl-propylenamine oxime (99mTc-HMPAO) brain SPECT study was used to evaluate regional cerebral blood flow to the calcified regions. There was markedly decreased perfusion to the basal ganglia bilaterally as well as decreased perfusion to the cerebral cortices that correlated well with the patient's clinical condition.

Technetium-99m ECD: a new brain imaging agent: in vivo kinetics and biodistribution studies in normal human subjects.

Lipophilic neutral 99mTc complexes of diaminedithiol (DADT) ligands cross the brain-blood barrier. A new derivative of DADT family, 99mTc ethyl cysteinate dimer (ECD) showed high brain uptake in nonhuman primates. We report here the in vivo kinetics and biodistribution results in 16 normal human subjects. Dynamic images of brain obtained for 10 min following an i.v. administration of [99mTc]ECD showed that the maximum 99mTc brain activity reached within 1 min and remained near that level for the next 10 min. The blood clearance of the tracer was very rapid and the activity remaining in blood after 5 min was less than 10%. Within 2 hr 50% of 99mTc activity was excreted in urine. Anterior and posterior total-body images were obtained at 5, 30, 60 min, 2, 4, 24, and 48 hr using a moving table at 20 cm/min. Percent injected dose was calculated for different organs and tissues. The brain uptake was 6.5 +/- 1.9% at 5 min postinjection and remained relatively constant over several hours. Two-compartment analysis of brain time-activity curve showed that 40% of brain activity washed out faster (T 1/2 = 1.3 hr) while the remaining 60% had a slower clearance rate (T 1/2 = 42.3 hr). Some of the tracer was excreted through the hepatobiliary system. Lung uptake and retention of [99mTc]ECD was negligible. Radiation dosimetry is favorable for the administration of up to 20-40 mCi of [99mTc]ECD. These results show that [99mTc]ECD is rapidly extracted and retained by the brain providing favorable conditions for single photon emission computed tomography imaging.

Brain single photon emission computed tomography: newer activation and intervention studies.

Single-photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) findings using non-xenon 133 tracers in combination with activation and intervention techniques are reviewed. Examination of the currently available data indicates that it is possible to detect the effects of a variety of activations and interventional procedures using SPECT rCBF with non-xenon 133 tracers. There are still many issues to be resolved before SPECT can reach the level of sophistication attained by xenon 133 and positron emission tomography in studying rCBF during activation or intervention. However, research to date indicates that SPECT rCBF studied with tracers other than xenon 133 has an excellent potential for increasing the ability to differentiate normal and pathological states.

An overview of the contribution of regional cerebral blood flow studies in cerebrovascular disease: is there a role for single photon emission computed tomography?

Regional cerebral blood flow (rCBF) findings and their application to cerebrovascular disease are reviewed. Although the coupling of cerebral blood flow and metabolism are best studied with positron emission tomography, single-photon emission computed tomography measurements of rCBF can contribute to patient management. Potential indications for the use of rCBF functional brain imaging include differential diagnosis, early prediction of late recovery in the late subacute and chronic phases of stroke (3 months or more postonset), and evaluation of vasospasm following subarachnoid hemorrhage.

Aphasics' sentence repetition behavior as a funciton of grammaticality.

Twenty asphasics repeated grammatical and ungrammatical sentences. Ungrammatical sentences were characterized by violations of syntactic and/or semantic structure. Aphasics repeated accurately more grammatical than ungrammatical sentences. Ungrammatical sentences with violations of syntactic structure were repeated less accurately than those with preserved syntax. Aphasics' repetition errors were classified as: incorrect repetition, inapropriate correction, morphological error, lexical deletion and substitution responses. Repetition errors appeared to result from performance deficits, such as reduced retention span and physiological limitations of the speech musculature. Results suggest that asphasics are to some extent guided by a greater residual linguistic knowledge or competence than might be inferred from their spontaneous production.

Acute ventricular hemorrhage in adults with hydrocephalus managed by corpus callosotomy and fenestration of the septum pellucidum. Report of three cases.

Three patients with hypertension-induced basal ganglia or thalamic hemorrhage and ventricular rupture underwent corpus callosotomy and fenestration of the septum pellucidum. A patient with a left thalamic hemorrhage underwent surgery on an emergency basis and made a complete physical recovery, although she retained mild psychomotor deficits. Another patient with a large right basal ganglia hemorrhage who also underwent surgery on an emergency basis retained a spastic left hemiparesis without evident psychomotor deficits. The third patient with a left thalamic and basal ganglia hemorrhage, who was initially awake and then lapsed into stupor days later, underwent surgery, but did not recover consciousness. Hydrocephalus was reversed and effectively controlled in all three patients without having to perform a shunt placement procedure.

Normal high-resolution cerebral 99mTc-HMPAO SPECT scans in symptomatic neonates exposed to cocaine.

Vascular constriction is said to account for a variety of clinical effects of cocaine. High-resolution 99mTc-hexamethylpropylene amine oxime single photon emission computed tomographic (SPECT) scans, which measure cerebral blood flow, were used to determine whether neonatal brain perfusion deficits are present in newborns with confirmed cocaine exposure. Normal, age-appropriate SPECT scans were found in 21 babies. Conventional neuroimaging was also performed when possible. All but one of the 14 magnetic resonance imaging (MRI) scans and one computed tomographic scan were normal. One MRI showed a mild delay in myelination. All but four neonates had behavioral or electroencephalographic abnormalities, and microcephaly was found in five of 21. The normal neonatal SPECT scans contrast with findings in adult cocaine users, which typically report abnormal findings of cerebral hypoperfusion. This study identifies a unique lack of corresponding cerebral vascular pathology in symptomatic neonates. It raises the possibility that many of these children can escape significant ischemic injury.

Single photon emission computerized tomography (SPECT) in detecting neurodegeneration in Huntington's disease.

Single photon emission computerized tomography (SPECT) studies were performed on 34 manifest Huntington's disease (HD) patients at various stages of clinical pathology ranging from early chorea to late dystonia with or without signs of dementia and 12 pre-symptomatic patients with abnormal terminal CAG expansions. Thirty HD patients with obvious clinical signs and seven pre-symptomatic patients without signs or symptoms of HD displayed selective caudate hypoperfusion by direct visual inspection. Such qualitative, selective striatal hypoperfusion patterns can be indicative of early and persistent metabolic changes in striatal neuropathology. SPECT studies can be useful in documenting early pre-clinical changes in patients with abnormal terminal CAG expansions and in confirming the presence of caudate pathology in patients with clinical signs of HD.

The effect of thalamic stimulation in processing of verbal stimuli in dichotic listening tasks: a case study.

In dichotic listening tasks, the (dominant) right ear's superiority in processing verbal stimuli has been attributed to its direct anatomic connection with the left dominant hemisphere. The role played by extralinguistic factors, such as attention and functional tuning of the associated cortical structures, has not been carefully examined. This investigation was undertaken to evaluate the effects of the left thalamic electric stimulation on the processing (recognition and recall) of dichotically presented CVC verbal stimuli in a patient being treated for chronic pain. We report the positive effects of electric stimulation (confirmed by increased subcortical metabolic activity using SPECT, a brain imaging technique) on the processing of dichotically presented verbal stimuli.

Use of SPECT to distinguish recurrent brain tumor from persistent activity at a craniotomy site.

A 50-year-old male underwent extensive left frontal lobe resection for a Grade II astrocytoma. Resection margins were free of tumor, and the patient suffered no significant postoperative neurologic deficits. One month later the patient was referred to radiation therapy for further evaluation and possible treatment. Unenhanced and enhanced transmission computed tomograms (CT) were interpreted as suspicious for recurrent tumor. However, using CT, which is essentially an anatomic technique, may not allow one to distinguish between surgical changes and the morbid anatomic findings of recurrent tumor. Because Tc-99m DTPA will cross the blood-brain barrier at sites of active intercranial disease, brain scintigraphy frequently is of value in distinguishing between recurrent tumor with an unstable blood-brain barrier and healed surgical changes with a stabilized blood-brain barrier. Therefore, clinicians requested that a Tc-99m DTPA brain scintigram be performed so as to distinguish between active disease and healed surgical changes.

CT, magnetic resonance imaging, and SPECT iodine-123 iodoamphetamine imaging of a patient with progressive cognitive deterioration.

A case of progressive cognitive deterioration is presented in which I-123 iodoamphetamine SPECT brain imaging was of value in confirming the clinical diagnosis of Alzheimer's disease.