Localization of epileptic foci with postictal single photon emission computed tomography

Effective surgical treatment of patients with intractable complex partial seizures depends on accurate preoperative seizure focus localization. We evaluated seizure localization with interictal and immediate postictal single photon emission computed tomographic images of cerebral perfusion using technetium-99m-hexamethyl-propyleneamineoxime (99mTc-HMPAO) in comparison with conventional ictal electroencephalographic (EEG) localization. Thirty-two patients with intractable complex partial seizures were studied. The mean delay from seizure onset to injection was 6.3 +/- 5.3 (SD) minutes. Independent blinded observers assessed the scans for interictal hypoperfusion and postictal focal hyperperfusion. Interictal scans alone were unreliable, indicating the correct localization in 17 patients (53%) and an incorrect site in 3 (9%). When interictal and postictal scans were interpreted together, the focus was correctly localized in 23 patients (72%). There was 1 false-positive study, and 8 patients had inconclusive changes, including 2 with inconclusive depth EEG studies. Postictal hyperperfusion was predominantly mesial temporal and frequently associated with hypoperfusion of lateral temporal cortex. Secondarily generalized seizures tended to show focal hyperperfusion less often than complex partial seizures did (Fisher's exact test p = 0.09). Combined interictal and immediate postictal single photon emission computed tomography with 99mTc-HMPAO is a useful noninvasive technique for independent confirmation of electrographic seizure localization. It may provide a suitable alternative to the use of depth electrode studies for confirmation of surface EEG findings in many patients with complex partial seizures.     

PET与发作间期癫痫灶定位

我们用￣~(１８)Ｆ－ＦＤＧ－ＰＢＴ显像对１２６例癫痫患者进行了发作间期癫痫灶定位，男８１例，女４５例，年龄２～５６岁，其中１１０例（８７．３％）在ＰＥＴ上可发现明显相对低代谢区，而ＭＲＩ或ＣＴ仅３２例发现异常，头皮ＥＥＧ有１０２例异常，但无明确定位价值。我们认为，￣１８Ｆ－ＦＤＧ－ＰＥＴ可通过观察脑组织内的葡萄糖代谢而进行癫痫灶定位，是无创伤性癫痫灶定位的最佳方法。     

Positron emission tomography

PET is a unique tool for the direct in vivo evaluation of physiologic processes within discrete areas of the brain. Thus far, its application to the study of schizophrenia has served to confirm the subtleties of this illness. However, PET does promise to increase our knowledge of the neurochemical anatomy of the normal and abnormal mind with respect to goal-directed behavior.     

Positron emission tomography radiochemistry

Factors that place constraints on radio-chemists who are seeking to design and develop radiopharmaceuticals for PET imaging studies include the short half-lives of 11C and 18F, minimum radiochemical yield and specific activity requirements, and high radiation fields that are associated with multi-Curie quantities of PET radionuclides. Nevertheless, during the past 20 years, considerable progress has been made in the development and application of a variety of PET radiotracers for a range of imaging studies in human subjects. We have highlighted a few areas of radiochemistry that focused on PET radiotracers that are described in this issue. Although the number of PET radiotracers synthesized is in the hundreds [6], much work remains to develop specific and useful PET radiotracers for a host of new and exciting noninvasive imaging applications.     

Positron emission tomography in neuropsychology

By positron emission tomography (PET) of 18F-2-fluoro-2-deoxy-D-glucose (FDG) local cerebral metabolic rate for glucose (LCMRGl) can be measured in man. Normal values in cerebral cortex and basal ganglia range from 35 to 50 mumol/100 g/min, the values in gray matter structures of the posterior fossa were 25-30 mumol/100 g/min, the lowest LCMRGl was found in the white matter (15-20 mumol/100 g/min). During sensory stimulation by various modalities functional activation increases LCMRGl in the respective special areas, while sleep decreases metabolic rate in all cortical and basal gray matter structures. In many neurological disorders CMRGl is altered in a disease-specific pattern. In dementia of the Alzheimer type CMRGl is impaired even in early stages with accentuation in the parieto-temporal cortex, while in multi-infarct dementia glucose uptake is mainly reduced in the multifocal small infarcts. In Huntington's chorea the most conspicuous changes are found in the caudate nucleus and putamen. In cases of focal lesions (e.g. ischemic infarcts) metabolic disturbances extend far beyond the site of the primary lesion and inactivation of metabolism is found in intact brain structures far away from the anatomical lesion. Additional applications of PET include determination of the metabolism of various substrates, of protein synthesis, of function and distribution of receptors, of tumor growth and of the distribution of drugs as well as the measurement of oxygen consumption, blood flow and blood volume.     

Localization of extratemporal epileptic foci during ictal single photon emission computed tomography.

We obtained single photon emission computed tomography (SPECT) scans with technetium-99M-hexamethyl-propylene-amine-oxime in 11 patients during 12 extratemporal partial seizures (9 simple partial, 3 complex partial). Ten ictal SPECT studies in 9 patients showed a focal region of hyperperfusion, which agreed with electrical seizure onset in 5 and with clinical seizure localization in 4 in whom ictal electroencephalography was not localized. Contralateral cerebellar and ipsilateral basal ganglia hyperperfusion was seen in 3 patients with a frontal lobe seizure focus. Ictal hyperperfusion was well circumscribed, unlike the diffuse hyperperfusion changes reported during temporal lobe seizures. This observation may indicate a different degree of seizure spread in temporal as opposed to extratemporal epilepsy. Because electroencephalographic localization is often elusive in extratemporal seizures, ictal SPECT may be very helpful for the localization of extratemporal foci.     

Positron emission tomography in Alzheimer's disease

Twenty-one patients with a clinical diagnosis of dementia of the Alzheimer's type (DAT) and 29 healthy, age-matched controls were studied using positron emission tomography (PET) and [18F]2-fluoro-2-deoxy-D-glucose to measure regional cerebral glucose consumption in the resting state. Reductions in ratio measures of relative metabolism in some parietal, temporal, and frontal regions were found in mild, moderate, and severe DAT groups. A significant increase in right/left metabolic asymmetry, particularly in parietal regions, also was seen in mild and moderate groups. Only in the severely demented patients was the absolute cerebral metabolic rate reduced significantly from control values. Fourteen patients had repeated PET studies, but only those patients with moderate to severe dementia showed a decline in IQ over 6 to 15 months. There were no significant changes in metabolic measures over time. PET is useful in quantifying regional cerebral dysfunction in DAT, even in the early stages of the disease.     

Positron emission tomography in Shy-Drager syndrome

We studied the nigrostriatal dopaminergic pathway in 3 patients with Shy-Drager syndrome, by using positron emission tomography and [18F]6-fluoro-1-dopa to determine whether their parkinsonism correlated with impaired functional integrity of the presynaptic nigrostriatal pathway. One patient had short duration of disease, mild parkinsonism, and a normal positron emission tomographic scan, suggesting pathological changes functionally distal to the nigrostriatal pathway. Two patients with longer duration of disease had more severe parkinsonism and reduced [18F]6-fluoro-1-dopa uptake, suggesting impaired nigrostriatal dopaminergic function with progression of Shy-Drager syndrome.     

Positron emission tomography in movement disorders

Positron emission tomography provides a method for the quantitation of regional function within the living human brain. Studies of cerebral metabolism and blood flow in patients with Huntington's disease, Parkinson's disease and focal dystonia have revealed functional abnormalities within substructures of the basal ganglia. Recent developments permit assessment of both pre-synaptic and post-synaptic function in dopaminergic pathways. These techniques are now being applied to studies of movement disorders in human subjects.     

Positron emission tomography in generalized seizures

We used 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to study nine patients with clinical absence or generalized seizures. One patient had only absence seizures, two had only generalized tonic-clonic seizures, and six had both seizure types. Interictal scans in eight failed to reveal focal or lateralized hypometabolism. No apparent abnormalities were noted. Two patients had PET scans after isotope injection during hyperventilation-induced generalized spike-wave discharges. Diffusely increased metabolic rates were found in one compared with an interictal scan, and in another compared with control values. Another patient had FDG injected during absence status: EEG showed generalized spike-wave discharges (during which she was unresponsive) intermixed with slow activity accompanied by confusion. Metabolic rates were decreased, compared with the interictal scan, throughout both cortical and subcortical structures. Interictal PET did not detect specific anatomic regions responsible for absence seizure onset in any patient, but the results of the ictal scans did suggest that pathophysiologic differences exist between absence status and single absence attacks.     

Positron emission tomography in neurological diseases

Positron emission tomography (PET) is the study of human physiology by electronic detection of positron-emitting radiopharmaceuticals. It is one of the noninvasive technologies that can measure the metabolic and functional activity of living tissue. Positron emission tomography finds its clinical applications in broadly three specialties--oncology, cardiology, and neurology. The current review focuses on its indications in neurological diseases. Recently published literature on the use of PET in neurology has been thoroughly analyzed. Several reports regarding the usage of PET in epilepsy, stroke, dementia, and movement disorders are available. Positron emission tomography does not appear to be useful as a primary or sole imaging technique in these conditions. On the other hand, it is useful in very specific situations, which have been elaborated in the review. It is also noteworthy that PET is complementary to the computed tomography/magnetic resonance imaging findings and data obtained from combining these modalities can be valuable in situations such as localization of the epileptogenic focus in cases of refractory epilepsy or for prediction of the outcome after thrombolysis in acute ischemic stroke. The major handicaps in widespread use of PET appear to be its lack of availability and its relatively high cost. Nevertheless, a review such as this would be helpful in judiciously selecting those patients who would benefit from undergoing a PET scan, at a time when PET imaging facility is likely to be available soon in the Indian private sector.     

Positron emission tomography in degenerative dementias

Positron emission tomography demonstrates different abnormalities of cerebral metabolism or characteristic disturbances of neurotransmission systems in "cortical" and "subcortical" dementias. Those patterns may reflect the underlying anatomopathology, but may also give clues to the pathophysiology of a disease and its symptoms.     

Positron emission tomography in pediatric neurology

Positron emission tomography (PET) is an accurate and relatively noninvasive way of studying brain activity using systemically administered tracers labeled with positron emitting isotopes. In pediatric neurology, it has great scope not only to elucidate the complexities of the developing brain but also to understand disease processes and characterize biological risk factors. Its greatest clinical utility lies in the field of epilepsy where it is used (in patients with intractable partial epilepsy) to localize epileptogenic foci for surgical resection. In addition, functional brain mapping using PET is increasingly being used to reliably and accurately identify speech and sensory-motor areas to minimize postoperative morbidity. PET is also useful in evaluating neurodegenerative disorders and cognitive abnormalities when magnetic resonance imaging scans are unrevealing. The technology continues to progress rapidly through improvements in imaging and radiopharmacology with potential applications in neurooncology, cerebral vascular disease, and metabolic diseases.     

Positron emission tomography in manganese intoxication

We employed 6-fluorodopa to study the integrity of the nigrostriatal dopaminergic projection by positron emission tomography in 4 subjects with clinical features of mild parkinsonism caused by exposure to manganese. The 6-fluorodopa scans were normal. This finding suggests that in early manganism sufficient to cause parkinsonian deficits, damage may occur in pathways postsynaptic to the nigrostriatal system, probably involving striatal or pallidal neurons. Fluorodeoxyglucose scans showed decreased cortical glucose metabolism, the significance of which is discussed.     

Positron emission tomography in Rasmussen's encephalitis

This report presents unusual positron emission tomography findings in an 11-year-old male with Rasmussen's encephalitis. This patient underwent fluorine-18 fluorodeoxyglucose positron emission tomography to localize his ictal focus before surgical consideration. Positron emission tomography disclosed marked hypermetabolism in the left cerebral hemisphere and basal ganglia with subnormal right cerebral activity and crossed cerebellar diaschisis. The heterogeneous distribution of metabolism suggests a combination of areas in different stages of ictal and postictal involvement. The hypermetabolic region in the left hemisphere was larger in size and extent (now including the left frontoparietal lobe) than the sole hypermetabolic left temporal lobe on his positron emission tomography from 2 years ago. While this positron emission tomography pattern of progression appears most commonly in Rasmussen's encephalitis case studies, few serial reports exist. The complex positron emission tomography findings of this case emphasize the importance of knowing the history of recent seizures, seizure type, clinical status at time of injection, and electroencephalographic correlation before interpreting functional neuroimaging studies. Finally, positron emission tomography studies can help clarify whether patients with Rasmussen's encephalitis with dominant hemisphere involvement are appropriate candidates for surgery or not.     

Positron emission tomography in Creutzfeldt-Jakob disease

Regional cerebral glucose metabolism was studied in a 73-year-old woman with autopsy-confirmed Creutzfeldt-Jakob disease, using positron emission tomography of 2-(18F)fluorodeoxyglucose. Regional absolute values were analyzed in 14 partially overlapping slices. Clinically, the patient was in an advanced stage of disease when positron emission tomographic scans revealed severe, diffuse hypometabolism, and neuropathological findings showed diffuse spongiform changes throughout the brain, with neuronal cell loss being obvious only in the cerebellum. Computed tomography was unremarkable for age, whereas the positron emission tomographic results were in accordance with histological findings and the patient's clinical condition. This article suggests that positron emission tomography depicts neuronal dysfunction rather than neuronal cell loss.     

PET定位伽玛刀治疗癫痫性精神障碍的临床研究

目的 探讨PET定位伽玛刀放射外科治疗癫痫性精神障碍(EPP)的方法及疗效.方法 45例EPP患者依据18F-2-氟-2-脱氧葡萄糖(FDG)PET显像及癫痫发作特点、脑电图、MRI等检查定位致痫灶,依据定位明确情况及患者EPP类型将病例分为2组:(1)发作性精神障碍组(PEP组),共25例,均行癫痫灶伽玛刀治疗.(2)非发作性精神障碍组(NEP),共20例,其中完成致痫灶定位的共16例(NEPc组),行癫痫灶联合胼胝体和双侧扣带回前部伽玛刀治疗;未明确定位的4例(NEPs组)仅行脑深部核团伽玛刀毁损. 结果 精神症状临床疗效总评量表(CGI)疗效指数总体良好率达到62.2％,其中PEP组和NEPs组良好率分别为72.0％和75.0％,明显高于NEPc组的43.8％.62.2％(28/45)癫痫预后达到Wieser Ⅰ～Ⅱ级,20.0％(9/45)达到Ⅲ～Ⅳ级,有效率为82.2％,其中NEPs组有效率为25.0％ (1/4),明显低于PEP和NEPc组的88.0％和87.5％. 结论 药物难治的癫痫性精神障碍患者通过伽玛刀治疗可以达到良好的效果,PEP患者可以行单纯癫痫灶伽玛射线照射,NEP患者应当联合癫痫灶伽玛射线照射及脑深部核团伽玛刀毁损的方法治疗.     

Positron emission tomography imaging of neuroinflammation

In the diseased brain, upon activation microglia express binding sites for synthetic ligands designed to recognize the 18-kDa translocator protein TP-18, which is part of the so-called peripheral benzodiazepine receptor complex. PK11195 [1-(2-chlorophenyl)-N-methyl-N- (1-methylpropyl)-3-isoquinoline carboxamide], the prototype synthetic ligand, has been widely used for the functional characterization of TP-18. Its cellular source in activated microglia has been established using high-resolution, single-cell autoradiography with the R-enantiomer [³H](R)-PK11195. Radiolabeled [¹¹C](R)-PK11195 has been used to image active brain disease with positron emission tomography. Consistent with experimental and postmortem observations of a characteristically distributed pattern of microglia activation in areas of focal pathology, as well as in anterograde and retrograde projection areas, the in vivo regional [¹¹C](R)-PK11195 signal is found in active focal lesions and over time also along the affected neural tracts and their respective cortical and subcortical projection areas. Thus, a profile of active disease emerges that matches some of the typical distribution patterns known from structural neuroimaging techniques, but additionally shows involvement of brain regions linked through neural pathways. In the context of cell-based in vivo neuropathology, the image data are thus best interpreted in the context of the emerging cellular understanding of brain disease or damage, rather than the definitions of clinical diagnosis. One important observation, borne out by experiment, is the long latency with which activated microglia or increased PK11195 retention appear to gradually emerge and remain in distal areas secondarily affected by disease, supporting speculations that the presence of activated microglia is an important corollary of brain plasticity.