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. Present address: Department of Nuclear Medicine, The Queen Elizabeth Hospital, Woodville, South Australia, Australia     

In vivo imaging of muscarinic cholinergic receptors in temporal lobe epilepsy with a new PET tracer: [76Br]4-bromodexetimide.

Muscarinic acetyl cholinergic receptors (mAChRs) may be involved in the pathophysiology of partial epilepsy. Previous experimental and imaging studies have reported medial temporal abnormalities of mAChR in patients with medial temporal lobe epilepsy (MTLE). Suitable radiotracers for mAChR are required to evaluate these disturbances in vivo using PET. Dexetimide is a specific mAChR antagonist that has been labeled recently with 76Br. This first study in humans focused on regional distribution and binding kinetics of [76Br]4-bromodexetimide (BDEX) in patients with MTLE. METHODS: Ten patients with well-lateralized MTLE had combined MRI, 18F-fluorodeoxyglucose (FDG) PET and 76Br-BDEX PET studies. Time-activity curves were generated in PET-defined regions of interest, including the medial, polar and lateral regions of the temporal lobe; the basal ganglia; the external and medial occipital cortex; and the white matter. RESULTS: The highest radioactivity concentration was observed in the basal ganglia and in the cortical regions, whereas radioactivity was lower in the white matter. On late images of PET studies, 76Br-BDEX uptake was statistically significantly decreased only in the medial temporal region ipsilateral to the seizure focus (1.37 +/-0.28, P < 0.01) as determined by FDG PET imaging, anatomic MRI and electroencephalogram correlation, compared with the contralateral medial temporal region (1.46 +/- 0.31). CONCLUSION: 76Br-BDEX concentration is reduced in the temporal lobe ipsilateral to the seizure focus in patients with MTLE. This preliminary study suggests that 76Br-BDEX is a suitable radiotracer for studies of mAChR in humans. Further studies are required to investigate the potential value of 76Br-BDEX PET in other neurological disorders with muscarinic disturbances.     

Presurgical identification of epileptic foci with iodine-123 iomazenil SPET: Comparison with brain perfusion SPET and FDG PET

Iodine-123 iomazenil (IMZ) has excellent characteristics for the quantification of central benzodiazepine receptor (BZR) binding with single-photon emission tomography (SPET). In order to evaluate the clinical value of IMZ SPET for presurgical identification of epileptic foci in patients with medically intractable seizures, we measured the binding potential (BP) of BZR using two IMZ SPET scans and compared the results with brain perfusion SPET and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). A total of ten patients with intractable partial epilepsy were examined by electroencephalography, magnetic resonance imaging, FDG PET, brain perfusion SPET and IMZ SPET. After neuroimaging examinations, five patients underwent selective surgery, and all of them have since been free of seizures. Two SPET scans were performed at 15 min (early) and 3 h (late) after intravenous injection of¹²³I-IMZ (167 MBq). Parametric images of the ligand transport (K ₁) and binding potential (BP) were calculated by the table look-up method, which is based on a three-compartment two-parameter model, using the standard arterial input function obtained by averaging of six normal volunteers' input functions. BP images delineated the epileptic foci more precisely than either FDG PET or ictal perfusion SPET. FDG PET showed widespread reduction, including the area surrounding the focus, and ictal increase in the cerebral blood flow was seen in possibly activated areas spread from the focus. In four epilepsy cases which originated from the mesial temporal lobe without lateral temporal abnormality, there was no significant decrease in the BP images in the lateral temporal structures, which showed decreased uptake of FDG. It is concluded that parametric images of BP with IMZ are valuable for precise presurgical localization of epileptic foci.     

Presurgical identification of epileptic foci with iodine-123 iomazenil SPET: comparison with brain perfusion SPET and FDG PET

. Iodine-123 iomazenil (IMZ) has excellent characteristics for the quantification of central benzodiazepine receptor (BZR) binding with single-photon emission tomography (SPET). In order to evaluate the clinical value of IMZ SPET for presurgical identification of epileptic foci in patients with medically intractable seizures, we measured the binding potential (BP) of BZR using two IMZ SPET scans and compared the results with brain perfusion SPET and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). A total of ten patients with intractable partial epilepsy were examined by electroencephalography, magnetic resonance imaging, FDG PET, brain perfusion SPET and IMZ SPET. After neuroimaging examinations, five patients underwent selective surgery, and all of them have since been free of seizures. Two SPET scans were performed at 15rmin (early) and 3rh (late) after intravenous injection of ¹²³I-IMZ (167rMBq). Parametric images of the ligand transport (K1) and binding potential (BP) were calculated by the table look-up method, which is based on a three-compartment two-parameter model, using the standard arterial input function obtained by averaging of six normal volunteers’ input functions. BP images delineated the epileptic foci more precisely than either FDG PET or ictal perfusion SPET. FDG PET showed widespread reduction, including the area surrounding the focus, and ictal increase in the cerebral blood flow was seen in possibly activated areas spread from the focus. In four epilepsy cases which originated from the mesial temporal lobe without lateral temporal abnormality, there was no significant decrease in the BP images in the lateral temporal structures, which showed decreased uptake of FDG. It is concluded that parametric images of BP with IMZ are valuable for precise presurgical localization of epileptic foci.     

Does technetium-99m bicisate image local brain metabolism in late ictal temporal lobe epilepsy?

Ictal increase in regional cerebral blood flow as judged by single-photon emission tomography (SPET) is a common phenomenon during focal epileptic seizures. Up to 2 min postictally, regional hyperperfusion is a consistent finding with technetium-99m hexamethylpropylene amine oxime (HMPAO) in temporal lobe epilepsy. A new ^99mTc-labelled lipophilic cerebral blood flow imaging agent, bicisate, has considerably longer radiochemical stability and yields better image quality than ^99mTc-HMPAO. In this report, we present the case of a 21-year-old female patient with temporal lobe complex partial seizures. Magnetic resonance imaging revealed right hippocampal sclerosis. A dose of 550 MBq of ^99mTc-bicisate was injected 35 s after the onset of a seizure during intracranial EEG-videotelemetry. At the moment of injection, subdural EEG demonstrated the beginning of late ictal discharges and postictal suppression in the right temporomesial areas. Late ictal SPET images showed marked right fronto-temporo-parietal hypoactivity. The interictal SPET study clearly showed right frontotemporal hypoactivity. These preliminary data suggest that ^99mTc-bicisate shows late ictal/early postictal hypoactivity which might represent the primary change in neuronal metabolism rather than the secondary change in cerebral blood flow. Correspondence to: J.T. Kuikka     

MR volumetry of the entorhinal, perirhinal, and temporopolar cortices in drug-refractory temporal lobe epilepsy

BACKGROUND AND PURPOSE: The occurrence of damage in the entorhinal, perirhinal, and temporopolar cortices in unilateral drug-refractory temporal lobe epilepsy (TLE) was investigated with quantitative MR imaging. METHODS: Volumes of the entorhinal, perirhinal, and temporopolar cortices were measured in 27 patients with unilateral drug-refractory TLE, 10 patients with extratemporal partial epilepsy, and 20 healthy control subjects. All patients with TLE were evaluated for epilepsy surgery and underwent operations. RESULTS: In left TLE, the mean volume of the ipsilateral entorhinal cortex was reduced by 17% (P <.001 compared with control subjects) and that of the ipsilateral temporopolar cortex by 17% (P <.05). In right TLE, the mean ipsilateral entorhinal volume was reduced by 13% (P < or =.01), but only in patients with hippocampal atrophy. Asymmetry ratios also indicated ipsilateral cortical atrophy. When each patient was analyzed individually, the volume of the ipsilateral hippocampus was reduced (> or = 2 SD from the mean of controls) in 63% and that of the entorhinal cortex in 52% of patients with TLE. Furthermore, ipsilateral entorhinal (left: r = 0.625, P <.001; right: r = 0.524, P < or =.01), perirhinal (left: r = 0.471, P <.05), and temporopolar (right: r = 0.556, P <.01) volumes correlated with ipsilateral hippocampal volumes. There was no association, however, with clinically or pathologically identified causes of epilepsy, duration of epilepsy, or age at onset of epilepsy. Mean cortical volumes were unaffected in extratemporal partial epilepsy. CONCLUSION: Subpopulations of patients with unilateral TLE have ipsilateral damage in the entorhinal and temporopolar cortices. The damage is associated with hippocampal damage.     

Ictal technetium-99m ethyl cysteinate dimer single-photon emission tomographic findings and propagation of epileptic seizure activity in patients with extratemporal epilepsies

Although ictal single-photon emission tomography (SPET) with technetium-99m ethyl cysteinate dimer (ECD) has a well-established role in the diagnostic evaluation of patients with temporal lobe epilepsy who are being considered for epilepsy surgery, its use in cases of extratemporal epilepsy is still limited. We investigated the influence of the propagation of extratemporal epileptic seizure activity on the regional increase in cerebral blood flow, which is usually associated with epileptic seizure activity. Forty-two consecutive patients with extratemporal epilepsies were prospectively evaluated. All patients underwent ictal SPET studies with simultaneous electroencephalography (EEG) and video recordings of habitual seizures and imaging studies including cranial magnetic resonance imaging and positron emission tomography with 2-[¹⁸F]-fluoro-2 deoxy-d-glucose. Propagation of epilptic seizure activity (PESA) was defined as the absence of hyperperfusion on ictal ECD SPET in the lobe of seizure onset, but its presence in another ipsilateral or contralateral lobe. Observers analysing the SPET images were not informed of the other results. PESA was observed in 8 of the 42 patients (19%) and was ipsilateral to the seizure onset in five (63%) of these eight patients. The time between clinical seizure onset and injection of the ECD tracer ranged from 14 to 61 s (mean 34 s). Seven patients (88%) with PESA had parieto-occipital epilepsy and one patient had a frontal epilepsy. PESA was statistically more frequent in patients with parieto-occipital lobe epilepsies (58%) than in the remaining extratemporal epilepsy syndromes (3%) (P<0.0002). These findings indicate that ictal SPET studies require simultaneous EEG-video recordings in patients with extratemporal epilepsies. PESA should be considered when interpreting ictal SPET studies in these patients. Patients with PESA are more likely to have parieto-occipital lobe epilepsy than seizure onset in other extratemporal regions. Received 14 August and in revised form 31 October 1997     

Monoamine oxidase B single-photon emission tomography with [123I]Ro 43-0463: imaging in volunteers and patients with temporal lobe epilepsy

Imaging of monoamine oxidase of subtype B (MAO B) is of interest in various neurological diseases. In the past non-invasive assessment of MAO B has only been possible with positron emission tomography (PET) ligands. Given the limited availability of PET, a single-photon emission tomography (SPET) ligand would be desirable. In this study SPET imaging with the new MAO B inhibitor [¹²³I]Ro 43-0463 was performed in five volunteers and nine patients with temporal lobe epilepsy (TLE). In two volunteers a second study was performed 12 h following blockade with deprenyl. In the TLE patients the tracer was administered as bolus (n = 4) or as prolonged infusion (n = 5). The regional uptake pattern correlated well with the known distribution of MAO B. In the two blocking studies ligand uptake was substantially reduced compared with baseline. In the TLE patients increased uptake was found in the ipsilateral mesial temporal lobe and, surprisingly, in the ipsilateral putamen. This study indicates the potential of the new SPET ligand [¹²³I]Ro 43-0463 to map MAO B concentration in the human brain. The new finding of increased MAO B in the putamen of TLE patients needs further studies to elucidate its exact pathophysiology. Received 2 October and in revised form 29 December 1997     

Imaging findings in hippocampal sclerosis: correlation with pathology

We evaluated the ability of preoperative radiologic imaging to detect hippocampal sclerosis in 31 patients who underwent surgery for intractable epilepsy. Hippocampal sclerosis is commonly associated with surgically treatable temporal lobe epilepsy. It is pathologically described as neuronal cell loss with associated gliosis in the hippocampus. While previous reports have correlated imaging results with clinical or qualitative histologic findings, this study used quantitative pathologic criteria (neuronal cell density) to diagnosis hippocampal sclerosis. We focused our study on the 11 patients with cryptogenic temporal lobe epilepsy. Of these, nine had hippocampal sclerosis by pathologic criteria. MR findings included unilateral hippocampal atrophy, an increased signal in the hippocampus on long TR scans, and atrophy in the adjacent white matter and temporal lobe. Hippocampal atrophy was most frequently seen in the red nucleus plane on coronal scans, corresponding to the body of the hippocampus. We also compared hippocampal size on MR with neuronal density in surgical specimens of the 11 patients with cryptogenic temporal lobe epilepsy. A statistically significant correlation was found between MR size and neuronal density in CA3 and CA4 of the cornu ammonis and the granular cell layer of the hippocampus. Since temporal lobectomy eliminated seizures in seven of nine patients with hippocampal sclerosis, preoperative diagnosis by MR has important therapeutic consequences.     

Effects of atropine treatment on in vitro and in vivo binding of 4-[125I]-dexetimide to central and myocardial muscarinic receptors

Upregulation of muscarinic cholinergic receptors (mAChR) after chronic atropine treatment has been described previously. The present study was designed to evaluate 4-iodine-125 dexetimide as an agent to determine changes in the number of mAChR. Rats were injected subcutaneously with atropine (500 mg/kg) either once or chronically, once daily for 10 days, and sacrificed 24 h later. In vitro binding assays with 4-[¹²⁵I]-dexetimide showed significant increases in the number of mAChR in cerebra (21%) and ventricles (45%) after chronic atropine treatment but not after acute treatment. The affinity of binding to cerebral and ventrical mAChR declined after acute and chronic atropine treatment. In vivo studies were carried out involving intravenous injection of 4-[¹²⁵I]-dexetimide 24 h after atropine treatment. Binding was markedly reduced in the brain and heart. Upregulation of mAChR, as seen in in vitro studies, could not be observed because of the remaining atropine. Occupancy of mAChR by atropine persisted as long as 7 days after one dose. The results of these studies indicate that 4-[¹²⁵I]-dexetimide binding reflects the effects of atropine on central and peripheral muscarinic cholinergic receptors in vitro and in vivo. Offprint requests to: U. Scheffel     

Discrepancy between blood flow and muscarinic receptor distribution in rat brain after middle cerebral artery occlusion

To clarify whether muscarinic acetylcholine receptor (mAChR) binding can be a viable muscarinic neuronal marker which provides therapeutic information different from perfusional information in global brain, we evaluated the discrepancy between the distribution of cerebral blood flow (CBF), mAChR and its live subtypes of messenger ribonucleic acid (mRNA) in the acute (n=9) and chronic (n=8) phases of a middle cerebral artery (MCA) occlusion model and in sham-operated controls (n=6). In the acute phase, regional CBF was markedly reduced in the MCA territory, whereas mAChR was not reduced and the mRNA was reduced only slightly. In the chronic phase, mAChR was reduced markedly in the infarcted lesion and the mRNA was also reduced. The mAChR was slightly reduced in the ipsilateral substantia nigra and pouline nucleus because of remote effects; however, regional CBF in the substantia nigra was slightly increased and did not change in the pontine nucleus. The discrepancy between CBF and mAChR was clarified, and the tendency toward a reduction in mRNA in the acute ischaemic region without a reduction in mAChR suggested the presence of cholinergic neurons which were viable but hypometabolic. It is concluded that mAChR imaging may be of value for the assessment of the viable cholinergic neuron density in vivo.     

癫痫病人MRI海马结构体积测定

目的测量正常成人及癫痫病人海马结构（ＨＦ）体积，探讨其在颞叶癫痫（ＴＬＥ）致痫灶定侧中的价值。材料与方法本组包括５２例正常成人及８９例癫痫病人，把病人分为三组：继发性癫痫４８例、特发颞叶外癫痫１５例、ＴＬＥ２６例，后者有２２例为顽固性癫痫。均作垂直于海马长轴的冠状位自旋回波（ＳＥ）序列Ｔ１加权像、ＴｕｒｂｏＳＥＴ２加权像，测量颞叶、ＨＦ体积和颞角、环池宽度，肉眼观察Ｔ２加权像海马信号强度改变。采用ＨＦ体积绝对值对ＴＬＥ定侧。结果获取了正常成人ＨＦ体积。２２例ＴＬＥＨＦ体积缩小，其中３例为双侧性；６例ＨＦ硬化经手术、病理证实，１例体积正常且致痫灶位于ＨＦ周围者ＨＦ硬化轻，８例其他类型癫痫病人ＨＦ体积略小，ＴＬＥ致痫灶定侧的敏感性为８５％，特异性为８７％。３例ＴＬＥ病人同侧前颞叶萎缩；部分ＴＬＥ病侧颞角、环池宽度增加；萎缩明显的ＨＦＴ２加权像信号弥漫性增高。结论ＨＦ体积缩小、Ｔ２加权像信号弥漫性增高是ＨＦ硬化萎缩的直接征象，与病变严重程度、致痫灶在颞叶的部位有关，前颞叶萎缩和颞角、环池增宽是ＨＦ硬化的辅助征象。ＨＦ萎缩不仅是颞叶癫痫的主要原因，也可能是其他类型癫痫发作的结果     

Methods for normalization of hippocampal volumes measured with MR.

PURPOSETo investigate the use of six cerebral measures as correlates for hippocampal volumes and, therefore, to enable normalized absolute hippocampal volumes to be calculated via two correction processes.METHODSHippocampal volumes and six cerebral measures were estimated from MR data in 20 control subjects. Three of these measures (the cranial volume, the cerebral volume, and the midsagittal cranial area) were then applied to a group of 32 control subjects, and regression analysis was performed to investigate the linear relationship between hippocampal volume and each measure. Division of hippocampal volume by cerebral measure and correction via a covariance calculation enabled corrected absolute hippocampal volumes to be determined for 32 control subjects and 23 patients with temporal lobe epilepsy.RESULTSCorrection processes reduced the variance in absolute hippocampal volumes in control subjects and enabled abnormally small absolute volumes to be defined. Of 11 patients with unilateral volume ratio abnormalities, 8 had unilateral abnormally small absolute hippocampal volumes. Of 12 patients with normal volume ratios, 4 had bilateral abnormally small absolute hippocampal volumes.CONCLUSIONCorrection processes can define absolute hippocampal volumes for correlation studies and may enable identification of unsuspected bilateral hippocampal volume loss.     

Decreased ipsilateral [123I]iododexetimide binding to cortical muscarinic receptors in unilaterally 6-hydroxydopamine lesioned rats

IntroductionDysfunction of the cholinergic neurotransmitter system is present in Parkinson’s disease, Parkinson’s disease related dementia and dementia with Lewy bodies, and is thought to contribute to cognitive deficits in these patients. In vivo imaging of the cholinergic system in these diseases may be of value to monitor central cholinergic disturbances and to select cases in which treatment with cholinesterase inhibitors could be beneficial. The muscarinic receptor tracer [¹²³I]iododexetimide, predominantly reflecting M₁ receptor binding, may be an appropriate tool for imaging of the cholinergic system by means of SPECT. In this study, we used [¹²³I]iododexetimide to study the effects of a 6-hydroxydopamine lesion (an animal model of Parkinson’s disease) on the muscarinic receptor availability in the rat brain.MethodsRats (n = 5) were injected in vivo at 10–13 days after a confirmed unilateral 6-hydroxydopamine lesion. Muscarinic receptor availability was measured bilaterally in multiple brain areas on storage phosphor images by region of interest analysis.ResultsAutoradiography revealed a consistent and statistically significant lower [¹²³I]iododexetimide binding in all examined neocortical areas on the ipsilateral side of the lesion as compared to the contralateral side. In hippocampal and subcortical areas, such asymmetry was not detected.ConclusionsThis study suggests that evaluation of muscarinic receptor availability in dopamine depleted brains using [¹²³I]iododexetimide is feasible. We conclude that 6-hydroxydopamine lesions induce a decrease of neocortical muscarinic receptor availability. We hypothesize that this arises from down regulation of muscarinic postsynaptic M₁ receptors due to hyperactivation of the cortical cholinergic system in response to dopamine depletion.Advances in knowledgeIn rats, dopamine depletion provokes a decrease in neocortical muscarinic receptor availability, which is evaluable by [¹²³I]iododexetimide imaging.Implications for patient careThis study may further underline the role of a dysregulated muscarinic system in patients with Lewy body disorders.     

Application of statistical parametric mapping to SPET in the assessment of intractable childhood epilepsy

Statistical parametric mapping (SPM) quantification and analysis has been successfully applied to functional imaging studies of partial epilepsy syndromes in adults. The present study evaluated whether localisation of the epileptogenic zone (determined by SPM) improves upon visually examined single-photon emission tomography (SPET) imaging in presurgical assessment of children with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE). The patient sample consisted of 24 children (15 males) aged 2.1–17.8 years (9.8±4.3 years; mean±SD) with intractable TLE or FLE. SPET imaging was acquired routinely in presurgical evaluation. All patient images were transformed into the standard stereotactic space of the adult SPM SPET template prior to SPM statistical analysis. Individual patient images were contrasted with an adult control group of 22 healthy adult females. Resultant statistical parametric maps were rendered over the SPM canonical magnetic resonance imaging (MRI). Two corresponding sets of ictal and interictal SPM and SPET images were then generated for each patient. Experienced clinicians independently reviewed the image sets, blinded to clinical details. Concordance of the reports between SPM and SPET images, syndrome classification and MRI abnormality was studied. A fair level of inter-rater reliability (kappa=0.73) was evident for SPM localisation. SPM was concordant with SPET in 71% of all patients, the majority of the discordance being from the FLE group. SPM and SPET localisation were concordant with epilepsy syndrome in 80% of the TLE cases. Concordant localisation to syndrome was worse for both SPM (33%) and SPET (44%) in the FLE group. Data from a small sample of patients with varied focal structural pathologies suggested that SPM performed poorly relative to SPET in these cases. Concordance of SPM and SPET with syndrome was lower in patients younger than 6 years than in those aged 6 years and above. SPM is effective in localising the potential epileptogenic zone but does not provide additional benefit beyond SPET in presurgical assessment of children with intractable epilepsy. The impact of different pathologies on the efficacy of SPM warrants further study.     

Increased anterior temporal lobe T2 times in cases of hippocampal sclerosis: a multi-echo T2 relaxometry study at 3 T

BACKGROUND AND PURPOSE: Increased T2 relaxation times in the ipsilateral hippocampus are present in patients with hippocampal sclerosis. Visual assessment of T2-weighted images of these patients suggests increased signal intensity in the anterior temporal lobe as well. Our aim was to assess hippocampal and anterior temporal T2 relaxation times in patients with partial epilepsy by using a new T2-relaxometry sequence implemented by using a 3-T General Electric imaging unit. METHODS: Coronal view T2 maps were generated by using an eight-echo Carr-Purcell-Meiboom-Gill sequence (TE, 28-231) with an acquisition time of 7 min on a 3-T General Electric Signa Horizon LX imaging unit. T2 relaxation times were measured in the hippocampus and anterior temporal lobe of 30 healthy control volunteers and 20 patients with partial epilepsy. RESULTS: For the 30 control volunteers, the mean hippocampal T2 relaxation time was 98 +/- 2.8 ms. In all measured areas, the asymmetry index was small (<0.01). For the 15 patients with independent evidence of hippocampal sclerosis established by visual, volumetric, and, when available, pathologic criteria, mean hippocampal T2 relaxation times were 118 +/- 7 ms (P <.0001) on the ipsilateral side and 101 +/- 4 ms (P =.005) on the contralateral side. The T2 values were also increased in the anterior temporal lobe (ipsilateral: 82 +/- 6 ms, P <.0001; contralateral: 79 +/- 6 ms, P =.01) as compared with the values for the control volunteers (75 +/- 3 ms). The five patients with focal cortical dysplasia had hippocampal T2 relaxation times that were not different from control values. CONCLUSION: T2 relaxometry at 3 T is feasible and useful and confirmed marked ipsilateral hippocampal signal intensity increase in patients with hippocampal sclerosis. Importantly, definite signal intensity change was also present in the anterior temporal lobe. T2 relaxometry is a sensitive means of identifying abnormalities in the hippocampus and other brain structures.     

Acetylcholine muscarinic receptors and response to anti-cholinesterase therapy in patients with Alzheimer's disease

An acetylcholine deficit remains the most consistent neurotransmitter abnormality found in Alzheimer's disease and various therapeutic agents have been targeted at this. In this study we investigated the action of Donepezil, a cholinesterase inhibitor that has few side-effects. In particular we set out to investigate whether muscarinic acetylcholine receptor (mAChR) availability influences the response to this therapy. We used the novel single-photon emission tomography (SPET) tracer (R, R)[(123)I]I-quinuclidinyl benzilate (R, R[(123)I]I-QNB), which has high affinity for the M1 subtype of mAChR. Regional cerebral perfusion was also assessed using technetium-99m hexamethylpropylene amine oxime. We investigated 20 patients on Donepezil treatment and ten age-matched controls. The results showed a reduction in (R, R)[(123)I]I-QNB binding in the caudal anterior cingulate in patients compared with controls and relatively high binding in the putamen and rostral anterior cingulate, suggesting a relative sparing of mAChR in these regions. The main finding of the study was that mAChR availability as assessed by (R, R)[(123)I]I-QNB binding did not distinguish responders from non-responders. Interestingly, we found that the extent of cognitive improvement showed no positive correlation with (R, R)[(123)I]I-QNB binding in any brain region but was inversely related to binding in the insular cortex. This suggests that, within the advised cognitive performance band for use of Donepezil, response is greater in those patients with evidence of a more marked cholinergic deficit. A larger study should investigate this.     

MR in temporal lobe epilepsy: analysis with pathologic confirmation.

PURPOSEWe evaluated the MR findings in patients with temporal lobe epilepsy to determine the predictive value of MR imaging in assessing patient outcome.METHODSMR studies from 186 of 274 consecutive patients who underwent temporal lobectomy for intractable epilepsy were reviewed retrospectively. Images were interpreted by an experienced neuroradiologist, who was blinded to the side of seizure activity and to pathologic findings.RESULTSMR imaging exhibited 93% sensitivity and 83% specificity in detecting hippocampal/amygdalar abnormalities (n = 121), and 97% sensitivity and 97% specificity in detecting abnormalities in the rest of the temporal lobe (n = 60). Abnormal high signal of the hippocampus on T2-weighted images had a sensitivity of 93% and specificity of 74% in predicting mesial temporal sclerosis (n = 115). The presence of hippocampal atrophy on MR correlated with the duration of seizures. Sensitivity and specificity of MR imaging in detecting temporal lobe tumors (n = 42) were 83% and 97%, respectively, based on abnormal signal and mass effect. After surgery, 63% of patients were seizure free and 28% had a significant reduction of seizure frequency at an average of 24 months (range, 12 to 78 months) after surgery. Patients with a single lesion in the anterior temporal lobe or hippocampus/amygdala had a better outcome than patients with multiple lesions (n = 22). Interrater agreement varied from 0.4 to 0.93, with best agreement for tumors or abnormal hippocampal signal on T2-weighted images.CONCLUSIONMR imaging is highly sensitive in detecting and locating abnormalities in the temporal lobe and the hippocampus/amygdala in patients with temporal lobe epilepsy. Hippocampal atrophy appears to correspond to the duration of seizure disorder.     

Reduced GABAA receptor density contralateral to a potentially epileptogenic MRI abnormality in a patient with complex partial seizures

Imaging cerebral GABA_A receptor density (GRD) with single-photon emission tomography (SPET) and iodine-123 iomazenil is highly accurate in lateralizing epileptogenic foci in patients with complex partial seizures of temporal origin. Limited knowledge exists on how iomazenil SPET compares with magnetic resonance imaging (MRI) in this regard. We present a patient with complex partial seizures in whom MRI had identified an arachnoid cyst anterior to the tip of the left temporal lobe. Contralaterally to this structural abnormality, interictal electroencephalography (EEG) performed after sleep deprivation disclosed an intermittent frontotemporal dysrhythmic focus with slow and sharp waves. On iomazenil SPET images GRD was significantly reduced in the right temporal lobe and thus contralaterally to the MRI abnormality, but ipsilaterally to the pathological EEG findings. These data suggest that iomazenil SPET may significantly contribute to the presurgical evaluation of epileptic patients even when MRI identifies potentially epileptogenic structural lesions.     

Three-dimensional fast low-angle shot imaging and computerized volume measurement of the hippocampus in patients with chronic epilepsy of the temporal lobe

This study investigated the use of three-dimensional fast low-angle shot (FLASH) imaging and computer-assisted morphometry for identifying hippocampal changes associated with unilateral temporal lobe seizures. Contiguous 3.1-mm coronal FLASH images were obtained in 28 patients with electroencephalographically verified left (n = 17) or right (n = 11) temporal lobe seizures and 28 age- and sex-matched control subjects. Hippocampal volumes were calculated with the use of a computerized mensuration system developed for detailed morphometric assessment. The results of a multivariate analysis of variance revealed a significant group difference by hemisphere interaction (F = 26.3, p less than .001). Significant reductions in left hippocampal volume (32%, p less than .001) were exhibited in patients with left temporal lobe seizures, and significant reductions in right hippocampal volume (35%, p less than .001) were seen in patients with right temporal lobe seizures. A discriminant analysis with the use of left and right hippocampal volumes classified patients with left temporal lobe seizures with 94% sensitivity and 73% specificity and patients with right temporal lobe seizures with 89% sensitivity and 94% specificity. The results of this study demonstrate that unilateral temporal lobe seizures are accompanied by significant reductions in hippocampal volume ipsilateral to the seizure focus. The use of FLASH imaging and computer-assisted morphometry of the hippocampus appears to provide valuable structural information for confirming the laterality of the electroencephalographic seizure focus.